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1.
Stroke ; 55(7): 1767-1775, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38748598

RESUMO

BACKGROUND: Studies comparing bridging intravenous thrombolysis (IVT) with direct endovascular therapy (EVT) in patients with acute ischemic stroke who present late are limited. We aimed to compare the clinical outcomes and safety of bridging IVT in patients with acute ischemic stroke due to anterior circulation large vessel occlusion who underwent EVT 6 to 24 hours after time last known well. METHODS: We enrolled patients with anterior circulation large vessel occlusion stroke and a National Institutes of Health Stroke Scale score of ≥6 from 20 centers across 10 countries in the multicenter retrospective CLEAR study (CT for Late Endovascular Reperfusion) between January 2014 and May 2022. We used inverse probability of treatment weighting modeling adjusted for clinical and imaging confounders to compare functional outcomes, reperfusion success, symptomatic intracranial hemorrhage, and mortality between EVT patients with and without prior IVT. RESULTS: Of 5098 patients screened for eligibility, we included 2749 patients, of whom 549 received bridging IVT before EVT. The timing of IVT was not recorded. Witnessed stroke onset and transfer rates were higher in the bridging IVT group (25% versus 12% and 77% versus 55%, respectively, P value for both <0.0001), and time intervals between stroke onset and treatment were shorter (time last known well-start of EVT median 560 minutes [interquartile range, 432-791] versus 724 minutes [interquartile range, 544-912]; P<0.0001). After adjustment for confounders, there was no difference in functional outcome at 3 months (adjusted common odds ratio for modified Rankin Scale shift, 1.03 [95% CI, 0.89-1.19]; P=0.72) or successful reperfusion (adjusted odds ratio, 1.19 [95% CI, 0.81-1.75]; P=0.39). There were no safety concerns associated with bridging IVT versus direct EVT (symptomatic intracranial hemorrhage: adjusted odds ratio, 0.75 [95% CI, 0.38-1.48]; P=0.40; mortality: adjusted odds ratio, 1.14 [95% CI, 0.89-1.46]; P=0.31). Results were unchanged when the analysis was limited to patients who received IVT >6 hours after last known well. CONCLUSIONS: In patients with an anterior circulation large vessel occlusion stroke who underwent EVT 6 to 24 hours from last known well, bridging IVT was not associated with a difference in outcomes compared with direct EVT. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04096248.


Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Terapia Trombolítica , Humanos , Masculino , Feminino , Idoso , AVC Isquêmico/terapia , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Procedimentos Endovasculares/métodos , Pessoa de Meia-Idade , Terapia Trombolítica/métodos , Resultado do Tratamento , Estudos Retrospectivos , Idoso de 80 Anos ou mais , Fibrinolíticos/uso terapêutico , Fibrinolíticos/administração & dosagem , Tempo para o Tratamento , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/terapia
2.
Stroke ; 55(2): 278-287, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38252759

RESUMO

BACKGROUND: The association between sex and outcome after endovascular thrombectomy of acute ischemic stroke is unclear. The aim of this study was to compare the clinical and safety outcomes between men and women treated with endovascular thrombectomy in the late 6-to-24-hour window period. METHODS: This multicenter, retrospective observational cohort study included consecutive patients who underwent endovascular thrombectomy of anterior circulation stroke in the late window from 66 clinical sites in 10 countries from January 2014 to May 2022. The primary outcome was the 90-day ordinal modified Rankin Scale score. Secondary outcomes included 90-day functional independence (FI), return of Rankin (RoR) to prestroke baseline, FI or RoR, symptomatic intracranial hemorrhage, and mortality. Multivariable and inverse probability of treatment weighting methods were used. We explored the interaction of sex with baseline characteristics on the outcomes ordinal modified Rankin Scale and FI or RoR. RESULTS: Of 1932 patients, 1055 were women and 877 were men. Women were older (77 versus 69 years), had higher rates of atrial fibrillation, hypertension, and greater prestroke disability, but there was no difference in baseline National Institutes of Health Stroke Scale score. Inverse probability of treatment weighting analysis showed no difference between women and men in ordinal modified Rankin Scale (odds ratio, 0.98 [95% CI, 0.79-1.21]), FI or RoR (odds ratio, 0.98 [95% CI, 0.78-1.22]), severe disability or mortality (odds ratio, 0.99 [95% CI, 0.80-1.23]). The multivariable analysis of the above end points was concordant. There were no interactions between baseline characteristics and sex on the outcomes of ordinal modified Rankin Scale and FI or RoR. CONCLUSIONS: In late presenting patients with anterior circulation stroke treated with endovascular thrombectomy in the 6 to 24-hour window, there was no difference in clinical or safety outcomes between men and women.


Assuntos
Fibrilação Atrial , AVC Isquêmico , Acidente Vascular Cerebral , Estados Unidos , Humanos , Feminino , Masculino , Caracteres Sexuais , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia
3.
Neuroradiology ; 66(4): 631-641, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38381145

RESUMO

PURPOSE: Our purpose was to assess the efficacy and safety of the pRESET LITE stent retriever (Phenox, Bochum, Germany), designed for medium vessel occlusion (MeVO) in acute ischemic stroke (AIS) patients with a primary MeVO. METHODS: We performed a retrospective analysis of the MAD MT Consortium, an integration of prospectively maintained databases at 37 academic institutions in Europe, North America, and Asia, of AIS patients who underwent mechanical thrombectomy with the pRESET LITE stent retriever for a primary MeVO. We subcategorized occlusions into proximal MeVOs (segments A1, M2, and P1) vs. distal MeVOs/DMVO (segments A2, M3-M4, and P2). We reviewed patient and procedural characteristics, as well as angiographic and clinical outcomes. RESULTS: Between September 2016 and December 2021, 227 patients were included (50% female, median age 78 [65-84] years), of whom 161 (71%) suffered proximal MeVO and 66 (29%) distal MeVO. Using a combined approach in 96% of cases, successful reperfusion of the target vessel (mTICI 2b/2c/3) was attained in 85% of proximal MeVO and 97% of DMVO, with a median of 2 passes (IQR: 1-3) overall. Periprocedural complications rate was 7%. Control CT at day 1 post-MT revealed a hemorrhagic transformation in 63 (39%) patients with proximal MeVO and 24 (36%) patients with DMVO, with ECASS-PH type hemorrhagic transformations occurring in 3 (1%) patients. After 3 months, 58% of all MeVO and 63% of DMVO patients demonstrated a favorable outcome (mRS 0-2). CONCLUSION: Mechanical thrombectomy using the pRESET LITE in a combined approach with an aspiration catheter appears effective for primary medium vessel occlusions across several centers and physicians.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Isquemia Encefálica/complicações , AVC Isquêmico/etiologia , Estudos Retrospectivos , Stents , Acidente Vascular Cerebral/etiologia , Trombectomia , Resultado do Tratamento , Idoso de 80 Anos ou mais
4.
Stroke ; 53(4): 1178-1189, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34634924

RESUMO

BACKGROUND: Aneurysmal persistence after flow diversion (FD) occurs in 5% to 25% of aneurysms, which may necessitate retreatment. There are limited data on safety/efficacy of repeat FD-a frequently utilized strategy in such cases. METHODS: A series of consecutive patients undergoing FD retreatment from 15 centers were reviewed (2011-2019), with inclusion criteria of repeat FD for the same aneurysm at least 6 months after initial treatment, with minimum of 6 months post-retreatment imaging. The primary outcome was aneurysmal occlusion, and secondary outcome was safety. A multivariable logistic regression model was constructed to identify predictors of incomplete occlusion (90%-99% and <90% occlusion) versus complete occlusion (100%) after retreatment. RESULTS: Ninety-five patients (median age, 57 years; 81% women) harboring 95 aneurysms underwent 198 treatment procedures. Majority of aneurysms were unruptured (87.4%), saccular (74.7%), and located in the internal carotid artery (79%; median size, 9 mm). Median elapsed time between the first and second treatment was 12.2 months. Last available follow-up was at median 12.8 months after retreatment, and median 30.6 months after the initial treatment, showing complete occlusion in 46.2% and near-complete occlusion (90%-99%) in 20.4% of aneurysms. There was no difference in ischemic complications following initial treatment and retreatment (4.2% versus 4.2%; P>0.99). On multivariable regression, fusiform morphology had higher nonocclusion odds after retreatment (odds ratio [OR], 7.2 [95% CI, 1.97-20.8]). Family history of aneurysms was associated with lower odds of nonocclusion (OR, 0.18 [95% CI, 0.04-0.78]). Likewise, positive smoking history was associated with lower odds of nonocclusion (OR, 0.29 [95% CI, 0.1-0.86]). History of hypertension trended toward incomplete occlusion (OR, 3.10 [95% CI, 0.98-6.3]), similar to incorporated branch into aneurysms (OR, 2.78 [95% CI, 0.98-6.8]). CONCLUSIONS: Repeat FD for persistent aneurysms carries a reasonable success/safety profile. Satisfactory occlusion (100% and 90%-99% occlusion) was encountered in two-thirds of patients, with similar complications between the initial and subsequent retreatments. Fusiform morphology was the strongest predictor of retreatment failure.


Assuntos
Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Mordida Aberta , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Estudos de Viabilidade , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/etiologia , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Mordida Aberta/etiologia , Mordida Aberta/terapia , Estudos Retrospectivos , Stents , Resultado do Tratamento
5.
Stroke ; 53(12): 3594-3604, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36252092

RESUMO

BACKGROUND: Reperfusion without functional independence (RFI) is an undesired outcome following thrombectomy in acute ischemic stroke. The primary objective was to evaluate, in patients presenting with proximal anterior circulation occlusion stroke in the extended time window, whether selection with computed tomography (CT) perfusion or magnetic resonance imaging is associated with RFI, mortality, or symptomatic intracranial hemorrhage (sICH) compared with noncontrast CT selected patients. METHODS: The CLEAR study (CT for Late Endovascular Reperfusion) was a multicenter, retrospective cohort study of stroke patients undergoing thrombectomy in the extended time window. Inclusion criteria for this analysis were baseline National Institutes of Health Stroke Scale score ≥6, internal carotid artery, M1 or M2 segment occlusion, prestroke modified Rankin Scale score of 0 to 2, time-last-seen-well to treatment 6 to 24 hours, and successful reperfusion (modified Thrombolysis in Cerebral Infarction 2c-3). RESULTS: Of 2304 patients in the CLEAR study, 715 patients met inclusion criteria. Of these, 364 patients (50.9%) showed RFI (ie, mRS score of 3-6 at 90 days despite successful reperfusion), 37 patients (5.2%) suffered sICH, and 127 patients (17.8%) died within 90 days. Neither imaging selection modality for thrombectomy candidacy (noncontrast CT versus CT perfusion versus magnetic resonance imaging) was associated with RFI, sICH, or mortality. Older age, higher baseline National Institutes of Health Stroke Scale, higher prestroke disability, transfer to a comprehensive stroke center, and a longer interval to puncture were associated with RFI. The presence of M2 occlusion and higher baseline Alberta Stroke Program Early CT Score were inversely associated with RFI. Hypertension was associated with sICH. CONCLUSIONS: RFI is a frequent phenomenon in the extended time window. Neither magnetic resonance imaging nor CT perfusion selection for mechanical thrombectomy was associated with RFI, sICH, and mortality compared to noncontrast CT selection alone. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04096248.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Estado Funcional , Estudos Retrospectivos , Resultado do Tratamento , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Reperfusão/métodos , Hemorragias Intracranianas , Procedimentos Endovasculares/métodos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia
6.
Radiology ; 304(2): 372-382, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35438564

RESUMO

Background The Woven EndoBridge (WEB) device was explicitly designed for wide-neck intracranial bifurcation aneurysms. Small-scale reports have evaluated the off-label use of WEB devices for the treatment of sidewall aneurysms, with promising outcomes. Purpose To compare the angiographic and clinical outcomes of the WEB device for the treatment of sidewall aneurysms compared with the treatment of bifurcation aneurysms. Materials and Methods A retrospective review of the WorldWideWEB Consortium, a synthesis of retrospective databases spanning from January 2011 to June 2021 at 22 academic institutions in North America, South America, and Europe, was performed to identify patients with intracranial aneurysms treated with the WEB device. Characteristics and outcomes were compared between bifurcation and sidewall aneurysms. Propensity score matching (PSM) was used to match by age, pretreatment ordinal modified Rankin Scale score, ruptured aneurysms, location of aneurysm, multiple aneurysms, prior treatment, neck, height, dome width, daughter sac, and incorporated branch. Results A total of 683 intracranial aneurysms were treated using the WEB device in 671 patients (median age, 61 years [IQR, 53-68 years]; male-to-female ratio, 1:2.5). Of those, 572 were bifurcation aneurysms and 111 were sidewall aneurysms. PSM was performed, resulting in 91 bifurcation and sidewall aneurysms pairs. No significant difference was observed in occlusion status at last follow-up, deployment success, or complication rates between the two groups. Conclusion No significantly different outcomes were observed following the off-label use of the Woven EndoBridge, or WEB, device for treatment of sidewall aneurysms compared with bifurcation aneurysms. The correct characterization of the sidewall aneurysm location, neck angle, and size is crucial for successful treatment and lower retreatment rate. © RSNA, 2022 See also the editorial by Hetts in this issue.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Roto/terapia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
7.
J Neurol Neurosurg Psychiatry ; 93(4): 360-368, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35078916

RESUMO

BACKGROUND: To analyse the clinical characteristics of COVID-19 with acute ischaemic stroke (AIS) and identify factors predicting functional outcome. METHODS: Multicentre retrospective cohort study of COVID-19 patients with AIS who presented to 30 stroke centres in the USA and Canada between 14 March and 30 August 2020. The primary endpoint was poor functional outcome, defined as a modified Rankin Scale (mRS) of 5 or 6 at discharge. Secondary endpoints include favourable outcome (mRS ≤2) and mortality at discharge, ordinal mRS (shift analysis), symptomatic intracranial haemorrhage (sICH) and occurrence of in-hospital complications. RESULTS: A total of 216 COVID-19 patients with AIS were included. 68.1% (147/216) were older than 60 years, while 31.9% (69/216) were younger. Median [IQR] National Institutes of Health Stroke Scale (NIHSS) at presentation was 12.5 (15.8), and 44.2% (87/197) presented with large vessel occlusion (LVO). Approximately 51.3% (98/191) of the patients had poor outcomes with an observed mortality rate of 39.1% (81/207). Age >60 years (aOR: 5.11, 95% CI 2.08 to 12.56, p<0.001), diabetes mellitus (aOR: 2.66, 95% CI 1.16 to 6.09, p=0.021), higher NIHSS at admission (aOR: 1.08, 95% CI 1.02 to 1.14, p=0.006), LVO (aOR: 2.45, 95% CI 1.04 to 5.78, p=0.042), and higher NLR level (aOR: 1.06, 95% CI 1.01 to 1.11, p=0.028) were significantly associated with poor functional outcome. CONCLUSION: There is relationship between COVID-19-associated AIS and severe disability or death. We identified several factors which predict worse outcomes, and these outcomes were more frequent compared to global averages. We found that elevated neutrophil-to-lymphocyte ratio, rather than D-Dimer, predicted both morbidity and mortality.


Assuntos
Isquemia Encefálica , COVID-19 , AVC Isquêmico , Acidente Vascular Cerebral , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/etiologia , Isquemia Encefálica/virologia , COVID-19/complicações , Humanos , AVC Isquêmico/epidemiologia , AVC Isquêmico/etiologia , AVC Isquêmico/virologia , Pessoa de Meia-Idade , Estudos Retrospectivos , SARS-CoV-2 , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/virologia , Trombectomia , Resultado do Tratamento
8.
Eur J Neurol ; 29(11): 3273-3287, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35818781

RESUMO

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.


Assuntos
Isquemia Encefálica , COVID-19 , Procedimentos Endovasculares , Acidente Vascular Cerebral , COVID-19/complicações , Estudos Transversais , Procedimentos Endovasculares/métodos , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
9.
J Stroke Cerebrovasc Dis ; 31(4): 106376, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35183984

RESUMO

BACKGROUND AND PURPOSE: Given recent evidence suggesting the clot composition may be associated with revascularization outcomes and stroke etiology, clot composition research has been a topic of growing interest. It is currently unclear what effect, if any, pre-thrombectomy thrombolysis has on clot composition. Understanding this association is important as it is a potential confounding variable in clot composition research. We retrospectively evaluated the composition of retrieved clots from ischemic stroke patients who did and did not receive pre-treatment tPA to study the effect of tPA on clot composition. MATERIALS AND METHODS: Consecutive patients enrolled in the Stroke Thromboembolism Registry of Imaging and Pathology (STRIP) were included in this study. All patients underwent mechanical thrombectomy and retrieved clots were sent to a central core lab for processing. Histological analysis was performed using Martius Scarlett Blue (MSB) staining and area of the clot was also measured on the gross photos. Student's t test was used for continuous variables and chi-squared test for categorical variables. RESULTS: A total of 1430 patients were included in this study. Mean age was 68.4±13.5 years. Overall rate of TICI 2c/3 was 67%. A total of 517 patients received tPA (36%) and 913 patients did not (64%). Mean RBC density for the tPA group was 42.97±22.62% compared to 42.80±23.18% for the non-tPA group (P=0.89). Mean WBC density for the tPA group was 3.74±2.60% compared to 3.42±2.21% for the non-tPA group (P=0.012). Mean fibrin density for the tPA group was 26.52±15.81% compared to 26.53±15.34% for the non-tPA group (P=0.98). Mean platelet density for the tPA group was 26.22±18.60% compared to 26.55±19.47% for the non-tPA group (P=0.75). tPA group also had significantly smaller clot area compared to non-tPA group. CONCLUSIONS: Our study 1430 retrieved emboli and ischemic stroke patients shows no interaction between tPA administration and clot composition. These findings suggest that tPA does not result in any histological changes in clot composition.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/tratamento farmacológico , Humanos , AVC Isquêmico/diagnóstico , AVC Isquêmico/tratamento farmacológico , Pessoa de Meia-Idade , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/tratamento farmacológico , Trombectomia/efeitos adversos , Ativador de Plasminogênio Tecidual/efeitos adversos
11.
Neuroradiology ; 63(2): 259-266, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32840681

RESUMO

PURPOSE: We report a multicenter experience using endovascular embolization as the first line approach for treatment of anterior cranial fossa (ACF) dural arteriovenous fistula (DAVF). METHODS: All patients with DAVFs located in the anterior cranial fossa who were treated with endovascular technique as a first line approach were included. Demographics, clinical presentation, angioarchitecture, strategy, complications, immediate angiographic, and follow-up results were included in the analysis. RESULTS: Twenty-three patients met the inclusion criteria (18 male and 5 female). Age ranged from 14 to 79 years (mean 53 years). Twelve patients presented with hemorrhage. Twenty-eight endovascular procedures were performed. The overall immediate angiographic cure rate after endovascular treatment was 82.6% (19/23 patients). The angiographic cure rate of the transvenous strategy was significantly superior to the transarterial strategy (p ≤ 0.001). There was 1 complication in 28 total procedures (3.6%). Angiographic follow-up was available in 21 out of the 23 patients with a mean of 25 months (range 2 to 108 months). In these 21 patients, the DAVF was completely cured in 20 (95%). At last follow-up, all patients had a modified Rankin scale (mRS) 0 to 2. CONCLUSION: Our experience suggests that endovascular treatment for ACF DAVFs has an acceptable safety profile with high rates of complete occlusion, particularly with transvenous approach. Whenever possible, transvenous approach should be preferred over transarterial approach as first line strategy.


Assuntos
Malformações Vasculares do Sistema Nervoso Central , Embolização Terapêutica , Procedimentos Endovasculares , Adolescente , Adulto , Idoso , Malformações Vasculares do Sistema Nervoso Central/diagnóstico por imagem , Malformações Vasculares do Sistema Nervoso Central/terapia , Fossa Craniana Anterior , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
12.
Mol Ther ; 28(2): 411-421, 2020 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-31813800

RESUMO

Global gene delivery to the CNS has therapeutic importance for the treatment of neurological disorders that affect the entire CNS. Due to direct contact with the CNS, cerebrospinal fluid (CSF) is an attractive route for CNS gene delivery. A safe and effective route to achieve global gene distribution in the CNS is needed, and administration of genes through the cisterna magna (CM) via a suboccipital puncture results in broad distribution in the brain and spinal cord. However, translation of this technique to clinical practice is challenging due to the risk of serious and potentially fatal complications in patients. Herein, we report development of a gene therapy delivery method to the CM through adaptation of an intravascular microcatheter, which can be safely navigated intrathecally under fluoroscopic guidance. We examined the safety, reproducibility, and distribution/transduction of this method in sheep using a self-complementary adeno-associated virus 9 (scAAV9)-GFP vector. This technique was used to treat two Tay-Sachs disease patients (30 months old and 7 months old) with AAV gene therapy. No adverse effects were observed during infusion or post-treatment. This delivery technique is a safe and minimally invasive alternative to direct infusion into the CM, achieving broad distribution of AAV gene transfer to the CNS.


Assuntos
Cisterna Magna/metabolismo , Dependovirus/genética , Expressão Gênica , Técnicas de Transferência de Genes , Vetores Genéticos/genética , Transdução Genética , Animais , Catéteres , Sistema Nervoso Central/metabolismo , Genes Reporter , Terapia Genética , Vetores Genéticos/administração & dosagem , Humanos , Injeções Espinhais , Imageamento por Ressonância Magnética , Modelos Animais , Ovinos , Cirurgia Assistida por Computador , Tomografia Computadorizada por Raios X , Transgenes , Gravação em Vídeo
13.
Stroke ; 50(9): 2455-2460, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31318624

RESUMO

Background and Purpose- It remains unclear how experience influences outcomes after the advent of stent retriever technology. We studied the relationship between site experience and outcomes in the Trevo Acute Ischemic Stroke multicenter registry. Methods- The 24 sites that enrolled patients in the Trevo Acute Ischemic Stroke registry were trichotomized into low-volume (<2 cases/month), medium-volume (2-4 cases/month), and high-volume centers (>4 cases/month). Baseline features, imaging, and clinical outcomes were compared across the 3 volume strata. A multivariable analysis was performed to assess whether outcomes were influenced by site volumes. Results- A total of 624 patients were included and distributed as low- (n=188 patients, 30.1%), medium- (n=175, 28.1%), and high-volume (n=261, 41.8%) centers. There were no significant differences in terms of age (mean, 66±16 versus 67±14 versus 65±15; P=0.2), baseline National Institutes of Health Stroke Scale (mean, 17.6±6.5 versus 16.8±6.5 versus 17.6±6.9; P=0.43), or occlusion site across the 3 groups. Median (interquartile range) times from stroke onset to groin puncture were 266 (181.8-442.5), 239 (175-389), and 336.5 (221.3-466.5) minutes in low-, medium-, and high-volume centers, respectively (P=0.004). Higher efficiency and better outcomes were seen in higher volume sites as demonstrated by shorter procedural times (median, 97 versus 67 versus 69 minutes; P<0.001), higher balloon guide catheter use (40% versus 36% versus 59%; P≤0.0001), and higher rates of good outcome (90-day modified Rankin Scale [mRS], ≤2; 39% versus 50% versus 53.4%; P=0.02). There were no appreciable differences in symptomatic intracranial hemorrhage or 90-day mortality. After adjustments in the multivariable analysis, there were significantly higher chances of achieving a good outcome in high- versus low-volume (odds ratio, 1.67; 95% CI, 1.03-2.7; P=0.04) and medium- versus low-volume (odds ratio, 1.75; 95% CI, 1.1-2.9; P=0.03) centers, but there were no significant differences between high- and medium-volume centers (P=0.86). Conclusions- Stroke center volumes significantly influence efficiency and outcomes in mechanical thrombectomy.


Assuntos
Isquemia Encefálica/mortalidade , Hemorragias Intracranianas/mortalidade , Acidente Vascular Cerebral/mortalidade , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/terapia , Feminino , Humanos , Hemorragias Intracranianas/terapia , Isquemia/terapia , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Stents/efeitos adversos , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento
14.
Stroke ; 50(7): 1907-1910, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31138084

RESUMO

Background and Purpose- Nearly 30% of large vessel occlusion acute ischemic stroke clots are from an unknown source. We assessed histological clot composition in a series of patients with large vessel occlusion and investigated correlations between clot composition and stroke pathogenesis. Methods- As part of the multi-institutional STRIP registry (Stroke Thromboembolism Registry of Imaging and Pathology), consecutive emboli retrieved during mechanical thrombectomy were stained using Martius Scarlett Blue and analyzed using machine learning software. We assessed proportions of red blood cells, fibrin, platelets, and white blood cells. Correlations between clot components and stroke pathogenesis (large artery atherosclerosis, cardioembolism, and stroke of undetermined pathogenesis) were assessed using SPSS22. Results- One hundred five patients were included. The proportion of platelet-rich clots (55.0% versus 21.2%; P=0.005) and percentage of platelet content (22.1±4.2% versus 13.9±14.2%; P=0.03) was significantly higher in the large artery atherosclerosis group compared with the cardioembolic group. The proportion of platelet-rich clots (50.0% versus 21.2%; P=0.024) was also significantly higher in the cryptogenic group compared with cardioembolic cases. Large artery atherosclerosis and cryptogenic cases had a similar proportion of platelet-rich clots (55.0% versus 50.0%; P=0.636). There was no significant difference between stroke pathogenesis and the other major clot components. Conclusions- High platelet content of emboli is associated with a large artery atherosclerosis etiology of large vessel occlusion.


Assuntos
Arteriopatias Oclusivas/sangue , Plaquetas/patologia , Doenças Arteriais Cerebrais/sangue , Arteriosclerose Intracraniana/sangue , Embolia Intracraniana/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Contagem de Células Sanguíneas , Retração do Coágulo , Trombose Coronária/sangue , Feminino , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Sistema de Registros , Acidente Vascular Cerebral/sangue , Trombectomia , Tromboembolia/sangue , Tromboembolia/patologia
15.
Stroke ; 50(3): 697-704, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30776994

RESUMO

Background and Purpose- Mechanical thrombectomy has been shown to improve clinical outcomes in patients with acute ischemic stroke. However, the impact of balloon guide catheter (BGC) use is not well established. Methods- STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter study of patients with large vessel occlusion treated with the Solitaire stent retriever as first-line therapy. In this study, an independent core laboratory, blinded to the clinical outcomes, reviewed all procedures and angiographic data to classify procedural technique, target clot location, recanalization after each pass, and determine the number of stent retriever passes. The primary clinical end point was functional independence (modified Rankin Scale, 0-2) at 3 months as determined on-site, and the angiographic end point was first-pass effect (FPE) success rate from a single device attempt (modified Thrombolysis in Cerebral Infarction, ≥2c) as determined by a core laboratory. Achieving modified FPE (modified Thrombolysis in Cerebral Infarction, ≥2b) was also assessed. Comparisons of clinical outcomes were made between groups and adjusted for baseline and procedural characteristics. All participating centers received institutional review board approval from their respective institutions. Results- Adjunctive technique groups included BGC (n=445), distal access catheter (n=238), and conventional guide catheter (n=62). The BGC group had a higher rate of FPE following first pass (212/443 [48%]) versus conventional guide catheter (16/62 [26%]; P=0.001) and distal access catheter (83/235 [35%]; P=0.002). Similarly, the BGC group had a higher rate of modified FPE (294/443 [66%]) versus conventional guide catheter (26/62 [42%]; P<0.001) and distal access catheter (129/234 [55%]; P=0.003). The BGC group achieved the highest rate of functional independence (253/415 [61%]) versus conventional guide catheter (23/55 [42%]; P=0.007) and distal access catheter (113/218 [52%]; P=0.027). Final revascularization and mortality rates did not differ across the groups. Conclusions- BGC use was an independent predictor of FPE, modified FPE, and functional independence, suggesting that its routine use may improve the rates of early revascularization success and good clinical outcomes. Clinical Trial Registration- URL: https://www.clinicaltrials.gov . Unique identifier: NCT02239640.


Assuntos
Cateterismo/métodos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/estatística & dados numéricos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Angiografia Cerebral , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sistema de Registros , Stents , Resultado do Tratamento
16.
J Stroke Cerebrovasc Dis ; 28(11): 104319, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31402086

RESUMO

A 54-year-old male with metastatic melanoma, including a presumed brain metastasis underwent elective surgery when there was sudden onset of extensive bleeding upon resection. An emergent cerebral angiogram revealed a fusiform left posterior cerebral artery aneurysm. Malignant melanoma commonly metastasizes to the brain and has shown to assume a wide variety of appearances with involvement of almost any intracranial structures. The unexpected intraoperative finding required immediate action and strategic rethinking. The patient successfully underwent vessel sacrifice by means of coil embolization.


Assuntos
Aneurisma Roto/diagnóstico por imagem , Neoplasias Encefálicas/diagnóstico por imagem , Angiografia Cerebral , Erros de Diagnóstico , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética , Melanoma/diagnóstico por imagem , Neoplasias Cutâneas/diagnóstico por imagem , Aneurisma Roto/terapia , Neoplasias Encefálicas/secundário , Neoplasias Encefálicas/cirurgia , Embolização Terapêutica , Humanos , Aneurisma Intracraniano/terapia , Masculino , Melanoma/secundário , Melanoma/cirurgia , Metastasectomia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/cirurgia , Resultado do Tratamento
17.
Circulation ; 136(24): 2311-2321, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-28943516

RESUMO

BACKGROUND: Endovascular treatment with mechanical thrombectomy (MT) is beneficial for patients with acute stroke suffering a large-vessel occlusion, although treatment efficacy is highly time-dependent. We hypothesized that interhospital transfer to endovascular-capable centers would result in treatment delays and worse clinical outcomes compared with direct presentation. METHODS: STRATIS (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) was a prospective, multicenter, observational, single-arm study of real-world MT for acute stroke because of anterior-circulation large-vessel occlusion performed at 55 sites over 2 years, including 1000 patients with severe stroke and treated within 8 hours. Patients underwent MT with or without intravenous tissue plasminogen activator and were admitted to endovascular-capable centers via either interhospital transfer or direct presentation. The primary clinical outcome was functional independence (modified Rankin Score 0-2) at 90 days. We assessed (1) real-world time metrics of stroke care delivery, (2) outcome differences between direct and transfer patients undergoing MT, and (3) the potential impact of local hospital bypass. RESULTS: A total of 984 patients were analyzed. Median onset-to-revascularization time was 202.0 minutes for direct versus 311.5 minutes for transfer patients (P<0.001). Clinical outcomes were better in the direct group, with 60.0% (299/498) achieving functional independence compared with 52.2% (213/408) in the transfer group (odds ratio, 1.38; 95% confidence interval, 1.06-1.79; P=0.02). Likewise, excellent outcome (modified Rankin Score 0-1) was achieved in 47.4% (236/498) of direct patients versus 38.0% (155/408) of transfer patients (odds ratio, 1.47; 95% confidence interval, 1.13-1.92; P=0.005). Mortality did not differ between the 2 groups (15.1% for direct, 13.7% for transfer; P=0.55). Intravenous tissue plasminogen activator did not impact outcomes. Hypothetical bypass modeling for all transferred patients suggested that intravenous tissue plasminogen activator would be delayed by 12 minutes, but MT would be performed 91 minutes sooner if patients were routed directly to endovascular-capable centers. If bypass is limited to a 20-mile radius from onset, then intravenous tissue plasminogen activator would be delayed by 7 minutes and MT performed 94 minutes earlier. CONCLUSIONS: In this large, real-world study, interhospital transfer was associated with significant treatment delays and lower chance of good outcome. Strategies to facilitate more rapid identification of large-vessel occlusion and direct routing to endovascular-capable centers for patients with severe stroke may improve outcomes. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02239640.


Assuntos
Procedimentos Endovasculares , Isquemia/epidemiologia , Transferência de Pacientes/estatística & dados numéricos , Acidente Vascular Cerebral/epidemiologia , Trombectomia , Hospitais , Humanos , Isquemia/mortalidade , Isquemia/cirurgia , Estudos Prospectivos , Sistema de Registros , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/cirurgia , Análise de Sobrevida , Fatores de Tempo , Resultado do Tratamento
19.
Stroke ; 48(10): 2760-2768, 2017 10.
Artigo em Inglês | MEDLINE | ID: mdl-28830971

RESUMO

BACKGROUND AND PURPOSE: Mechanical thrombectomy with stent retrievers has become standard of care for treatment of acute ischemic stroke patients because of large vessel occlusion. The STRATIS registry (Systematic Evaluation of Patients Treated With Neurothrombectomy Devices for Acute Ischemic Stroke) aimed to assess whether similar process timelines, technical, and functional outcomes could be achieved in a large real world cohort as in the randomized trials. METHODS: STRATIS was designed to prospectively enroll patients treated in the United States with a Solitaire Revascularization Device and Mindframe Capture Low Profile Revascularization Device within 8 hours from symptom onset. The STRATIS cohort was compared with the interventional cohort of a previously published SEER patient-level meta-analysis. RESULTS: A total of 984 patients treated at 55 sites were analyzed. The mean National Institutes of Health Stroke Scale score was 17.3. Intravenous tissue-type plasminogen activator was administered in 64.0%. The median time from onset to arrival in the enrolling hospital, door to puncture, and puncture to reperfusion were 138, 72, and 36 minutes, respectively. The Core lab-adjudicated modified Thrombolysis in Cerebral Infarction ≥2b was achieved in 87.9% of patients. At 90 days, 56.5% achieved a modified Rankin Scale score of 0 to 2, all-cause mortality was 14.4%, and 1.4% suffered a symptomatic intracranial hemorrhage. The median time from emergency medical services scene arrival to puncture was 152 minutes, and each hour delay in this interval was associated with a 5.5% absolute decline in the likelihood of achieving modified Rankin Scale score 0 to 2. CONCLUSIONS: This largest-to-date Solitaire registry documents that the results of the randomized trials can be reproduced in the community. The decrease of clinical benefit over time warrants optimization of the system of care. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02239640.


Assuntos
Isquemia Encefálica/diagnóstico , Isquemia Encefálica/terapia , Trombólise Mecânica/normas , Sistema de Registros/normas , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Idoso , Isquemia Encefálica/epidemiologia , Estudos de Coortes , Feminino , Humanos , Masculino , Trombólise Mecânica/métodos , Pessoa de Meia-Idade , Estudos Prospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto/normas , Acidente Vascular Cerebral/epidemiologia , Tempo para o Tratamento/normas , Ativador de Plasminogênio Tecidual/administração & dosagem , Resultado do Tratamento
20.
Stroke ; 53(2): e47-e49, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34915737
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