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BACKGROUND AND PURPOSE: High revascularization rates in large-vessel occlusion strokes treated by mechanical thrombectomy are not always associated with good clinical outcomes. We evaluated predictors of functional dependence despite successful revascularization among patients with acute ischemic stroke treated with thrombectomy. METHODS: We analyzed the pooled data from the Multi Mechanical Embolus Removal in Cerebral Ischemia (MERCI), Thrombectomy Revascularization of Large Vessel Occlusions in Acute Ischemic Stroke (TREVO), and TREVO 2 trials. Successful revascularization was defined as thrombolysis in cerebral infarction score 2b or 3. Functional dependence was defined as a score of 3 to 6 on the modified Rankin Scale at 3 months. We assessed relationship of demographic, clinical, angiographic characteristics, and hemorrhage with functional dependence despite successful revascularization. RESULTS: Two hundred and twenty-eight patients with successful revascularization had clinical outcome follow-up. The rates of functional dependence with endovascular success were 48.6% for Trevo thrombectomy and 58.0% for Merci thrombectomy. Age (odds ratio, 1.04; 95% confidence interval, 1.02-1.06 per 1-year increase), National Institutes of Health Stroke Scale score (odds ratio, 1.08; 95% confidence interval, 1.02-1.15 per 1-point increase), and symptom onset to endovascular treatment time (odds ratio, 1.11; 95% confidence interval, 1.01-1.22 per 30-minute delay) were predictors of functional dependence despite successful revascularization. Symptom onset to reperfusion time beyond 5 hours was associated with functional dependence. All subjects with symptomatic intracranial hemorrhage had functional dependence. CONCLUSIONS: One half of patients with successful mechanical thrombectomy do not have good outcomes. Age, severe neurological deficits, and delayed endovascular treatment were associated with functional dependence despite successful revascularization. Our data support efforts to minimize delays to endovascular therapy in patients with acute ischemic stroke to improve outcomes. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00318071, NCT01088672, and NCT01270867.
Assuntos
Isquemia Encefálica/epidemiologia , Revascularização Cerebral , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/epidemiologia , Trombectomia , Terapia Trombolítica , Idoso , Idoso de 80 Anos ou mais , Infarto Encefálico/epidemiologia , Infarto Encefálico/fisiopatologia , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/fisiopatologia , Revascularização Cerebral/normas , Revascularização Cerebral/estatística & dados numéricos , Ensaios Clínicos como Assunto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Valor Preditivo dos Testes , Índice de Gravidade de Doença , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/normas , Trombectomia/estatística & dados numéricos , Terapia Trombolítica/normas , Terapia Trombolítica/estatística & dados numéricosRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to determine whether leukoaraiosis (LA) predicts hemorrhagic transformation and poor outcome in patients with acute ischemic stroke treated by mechanical thrombectomy. METHODS: We retrospectively analyzed patients with anterior circulation stroke treated with Merci devices and identified LA in the deep white matter (DWM) and periventricular white matter on the preintervention MR images. We dichotomized patients into those with moderate or severe LA in the DWM versus those without. Hemorrhage rates and outcomes were evaluated between 2 groups. We analyzed the association of moderate or severe LA with hemorrhagic transformation and poor outcome. RESULTS: Twenty-six of 105 patients had moderate or severe LA in the DWM. Patients with moderate or severe LA in the DWM were older, had more severe neurological deficits and worse outcome, had higher rates of hemorrhagic transformation and parenchymal hematoma, but had equivalent rates of hemorrhagic infarct and subarachnoid hemorrhage when compared with those without. Patients with only periventricular LA did not have a higher rate of parenchymal hematoma. Moderate or severe LA in the DWM was an independent predictor of hemorrhagic transformation (OR, 3.4; P=0.019) and parenchymal hematoma (OR, 6.3; P=0.005). Patients with parenchymal hematoma were less often independent (modified Rankin Scale≤2, 3.8% versus 32.5%; P=0.003) and had greater in-hospital mortality (50% versus 10.4%; P<0.001). CONCLUSIONS: Moderate or severe LA in the DWM increases the risk of parenchymal hematoma after Merci thrombectomy for patients with acute stroke. These findings require validation in a larger prospective study.
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Isquemia Encefálica/epidemiologia , Hematoma Subdural Crônico/epidemiologia , Leucoaraiose/epidemiologia , Trombólise Mecânica/efeitos adversos , Acidente Vascular Cerebral/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/terapia , Estudos de Coortes , Feminino , Hematoma Subdural Crônico/terapia , Humanos , Leucoaraiose/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Acidente Vascular Cerebral/terapiaRESUMO
Background: Circular RNAs (circRNAs) may involve the formation and rupture of intracranial aneurysms (IA). Inflammation plays a vital role in the development and progression of IA, which can be reflected by aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI). This study aims to evaluate the role of circRNAs as the blood inflammatory biomarker for unruptured IA (UIA) patients with AWE on HR-VWI. Methods: We analyzed the circRNA expression profiles in the peripheral blood samples among subjects from saccular UIA with AWE, UIA without AWE, and healthy controls by the circRNA microarray. The differential expression of hsa_circ_0007990 was assessed. We constructed the hsa_circ_0007990-microRNA-mRNA network and the regulatory axis of hub genes associated with the AWE in UIA. Results: Eighteen patients harboring saccular UIAs with HR VWI and five healthy controls were included. We found 412 differentially expressed circRNAs between UIA patients and healthy controls by circRNA microarray. Two hundred thirty-one circRNAs were significantly differentially expressed in UIA patients with AWE compared with those without AWE. Twelve upregulated circRNAs were associated with AWE of UIA, including hsa_circ_0007990, hsa_circ_0114507, hsa_circ_0020460, hsa_circ_0053944, hsa_circ_0000758, hsa_circ_0000034, hsa_circ_0009127, hsa_circ_0052793, hsa_circ_0000301 and hsa_circ_0000729. The expression of hsa_circ_0007990 was increased gradually in the healthy control, UIA without AWE, and UIA with AWE confirmed by RT-PCR (P<0.001). We predicted 4 RNA binding proteins (Ago2, DGCR8, EIF4A3, PTB) and period circadian regulator 1 as an encoding protein with hsa_circ_0007990. The hsa_circ_0007990-microRNA-mRNA network containing five microRNAs (miR-4717-5p, miR-1275, miR-150-3p, miR-18a-5p, miR-18b-5p), and 97 mRNAs was constructed. The five hub genes (hypoxia-inducible factor 1 subunit alpha, estrogen receptor 1, forkhead box O1, insulin-like growth factor 1, CREB binding protein) were involved in the inflammatory response. Conclusion: Differentially expressed blood circRNAs associated with AWE on HR-VWI may be the novel inflammatory biomarkers for assessing UIA patients. The mechanism of hsa_circRNA_0007990 for UIA progression needs to investigate further.
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Aneurisma Intracraniano , MicroRNAs , Humanos , Aneurisma Intracraniano/genética , RNA Circular/genética , MicroRNAs/genética , Proteínas de Ligação a RNA , Biomarcadores , RNA MensageiroRESUMO
Background and Purpose: Neutrophil-lymphocyte ratio (NLR) predicts clinical outcomes in patients with stroke. Aneurysm wall enhancement (AWE) on high-resolution vessel wall magnetic resonance imaging (HR-VWI) is an inflammation marker for intracranial aneurysm (IA). This study aims to evaluate the association of NLR as a peripheral blood inflammatory marker with circumferential AWE in patients with IA. Methods: We analyzed data of consecutive patients harboring IAs between September 2017 and December 2021 at our institution. The peripheral blood inflammatory indicators were compared between patients with ruptured and unruptured IAs. The presence of circumferential AWE in unruptured IA was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) on HR-VWI. We used the optimal cutoff value of 0.5 for CRstalk to differentiate circumferential AWE in unruptured IAs. We assessed the relationship of clinical, laboratory, and radiological characteristics with circumferential AWE and CRstalk ≥0.5 in unruptured IAs. Results: The study group was composed of one hundred and twenty-five patients with 142 IAs. NLR level at admission was significantly higher in patients with ruptured IAs than those with unruptured IAs (7.55 vs. 1.81; P < 0.001). AWE on HR-VWI was present in 30 patients with unruptured IAs (38.5%), including 12 with focal AWE and 18 with circumferential AWE. NLR (odds ratio (OR), 2.168; 95% CI, 1.149-4.088) and size (odds ratio, 1.370; 95% CI, 1.126-1.667) were independently associated with circumferential AWE in unruptured IA. NLR was also independently associated with circumferential AWE in small unruptured IA (<7 mm). Furthermore, NLR level at admission was associated with CRstalk ≥.5 in patients with unruptured IA. The optimal cutoff value of NLR for circumferential AWE was 1.86. Conclusion: NLR is a valuable peripheral blood inflammatory marker is more often in the rupture status of IA and was associated with circumferential AWE on HR-VWI in unruptured IA.
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BACKGROUND: Aneurysm wall enhancement on high-resolution vessel wall imaging (HR-VWI) may represent vessel wall inflammation for unruptured intracranial aneurysms (UIAs). Further evidence for the role of circumferential aneurysm wall enhancement (CAWE) in evaluating the instability of UIAs is required, especially in small aneurysms (<7 mm). METHODS: We analyzed patients with saccular UIAs who prospectively underwent HR-VWI on a 3.0 T MRI scanner in our center from September 2017 to August 2021. The presence of AWE was identified and quantitatively measured using the aneurysm-to-pituitary stalk contrast ratio (CRstalk) with maximal signal intensity value. The PHASES and ELAPSS scores were used to assess the risk of aneurysm rupture and growth. We evaluated the association of CAWE and CRstalk value with intracranial aneurysm instability. RESULTS: One hundred patients with 109 saccular UIAs were included in this study. Eighty-three UIAs (76.1%) had a size smaller than 7 mm. PHASES and ELAPSS scores were significantly higher in UIAs with CAWE than in UIAs without CAWE (p < .01). The association of CAWE with PHASES and ELAPSS scores remained in small UIAs (<7 mm). The optimal cutoff value of CRstalk for CAWE was 0.5. PHASES and ELAPSS scores were significantly higher in UIAs with CRstalk ≥0.5 than in UIAs with CRstalk <0.5 (p < .01). CONCLUSIONS: CAWE on HR-VWI is a valuable imaging marker for aneurysm instability in UIAs. CRstalk value ≥0.5 may be associated with a higher risk of intracranial aneurysm rupture and growth.
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Aneurisma Roto , Aneurisma Intracraniano , Aneurisma Roto/diagnóstico por imagem , Humanos , Inflamação , Aneurisma Intracraniano/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND AND PURPOSE: The benefit of endovascular revascularization of patients with acute ischemic stroke with middle cerebral artery (MCA) secondary division (M2) occlusions as compared with MCA trunk (M1) occlusions is not known. In this analysis, we compared revascularization status and clinical outcomes in patients with angiographically confirmed MCA M1 versus isolated M2 occlusions treated with mechanical thrombectomy using the Merci Retriever devices. METHODS: We retrospectively analyzed the pooled data of patients with MCA strokes from the Mechanical Embolus Removal in Cerebral Ischemia (MERCI) and Multi MERCI trials. Patient data were dichotomized into 2 groups: MCA M1 occlusions and isolated M2 occlusions. Baseline characteristics, revascularization rates, hemorrhage rates, complications, outcomes, and mortality were evaluated for both groups. RESULTS: Of 178 patients with MCA occlusion treated in the MERCI and Multi MERCI trials, 84.3% had M1 lesions and 15.7% had isolated M2 lesions. Patients with isolated M2 occlusions were revascularized at a higher rate, required a lower mean number of passes, and were associated with a trend toward shorter mean procedure time than patients with M1 occlusions. No statistically significant differences were found between M2 and M1 groups for symptomatic hemorrhage, clinically significant procedural adverse events, favorable 90-day outcome, or 90-day mortality, although in all instances, the M2 outcomes were numerically better than those in M1 subjects. In multivariate analysis, final revascularization was the strongest independent predictor of good outcome at 90 days. CONCLUSIONS: Patients with both MCA M1 occlusions and isolated M2 occlusions can achieve a relatively high rate of revascularization and favorable clinical outcomes after mechanical thrombectomy. In fact, patients with isolated M2 occlusions had a higher rate of revascularization, required fewer passes, and had no increased complications compared with patients with M1 occlusions.
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Isquemia Encefálica/cirurgia , Infarto da Artéria Cerebral Média/cirurgia , Embolia Intracraniana/cirurgia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Estudos de Coortes , Embolectomia/métodos , Feminino , Humanos , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/fisiopatologia , Embolia Intracraniana/complicações , Embolia Intracraniana/fisiopatologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trombectomia/métodos , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Intracranial mechanical thrombectomy is a therapeutic option for acute ischemic stroke patients failing intravenous tissue plasminogen activator (IV tPA). We compared patients treated by mechanical embolus removal in cerebral ischemia (MERCI) thrombectomy after failed IV tPA with those treated with thrombectomy alone. METHODS: We pooled MERCI and Multi MERCI study patients, grouped them either as failed IV tPA or non-IV tPA, and assessed revascularization rates, procedural complications, symptomatic hemorrhage rates, clinical outcomes, and mortality. We also evaluated outcomes stratified by the occlusion site and final revascularization. RESULTS: Among 305 patients, 48 failed, and 257 were ineligible for IV tPA. Nonresponders to IV tPA trended toward a higher revascularization rate (73% versus 63%) and less mortality (27.7% versus 40.1%) and had similar rates of symptomatic hemorrhage and procedural complications. Favorable 90-day outcomes were similar in failed and non-IV tPA patients (38% versus 31%), with no difference according to occlusion site. Among patients failing IV tPA, good outcomes tended to occur more frequently in revascularized patients (47.1% versus 15.4%), although this relationship was attributable solely to middle cerebral artery and not internal carotid artery occlusions, with no difference in mortality. Among IV tPA-ineligible patients, revascularization correlated with good outcome (47.4% versus 4.4%) and less mortality (28.5% versus 59.6%). CONCLUSIONS: The risks of hemorrhage and procedure-related complications after mechanical thrombectomy do not differ with respect to previous IV tPA administration. Thrombectomy after IV tPA achieves similar rates of good outcomes, a tendency toward lower mortality, and similar revascularization rates when stratified by clot location. Good outcomes correlate with successful revascularization except with internal carotid artery occlusions in tPA-nonresponders.
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Isquemia Encefálica , Doenças das Artérias Carótidas , Doenças Arteriais Cerebrais , Fibrinolíticos/administração & dosagem , Acidente Vascular Cerebral , Trombectomia , Ativador de Plasminogênio Tecidual/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/mortalidade , Isquemia Encefálica/terapia , Doenças das Artérias Carótidas/mortalidade , Doenças das Artérias Carótidas/terapia , Doenças Arteriais Cerebrais/mortalidade , Doenças Arteriais Cerebrais/terapia , Revascularização Cerebral/métodos , Intervalo Livre de Doença , Feminino , Fibrinolíticos/efeitos adversos , Hemorragia/etiologia , Hemorragia/mortalidade , Hemorragia/terapia , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/terapia , Taxa de Sobrevida , Ativador de Plasminogênio Tecidual/efeitos adversosRESUMO
BACKGROUND AND PURPOSE: Subarachnoid hemorrhage (SAH) is a potential hemorrhagic complication after endovascular intracranial recanalization. The purpose of this study was to describe the frequency and predictors of SAH in acute ischemic stroke patients treated endovascularly and its impact on clinical outcome. METHODS: Acute ischemic stroke patients treated with primary mechanical thrombectomy, intra-arterial thrombolysis, or both were analyzed. Postprocedural computed tomography and magnetic resonance images were reviewed to identify the presence of SAH. We assessed any decline in the National Institutes of Health Stroke Scale score 3 hours after intervention and in the outcomes at discharge. RESULTS: One hundred twenty-eight patients were treated by primary thrombectomy with MERCI Retriever devices, whereas 31 were treated by primary intra-arterial thrombolysis. Twenty patients experienced SAH, 8 with pure SAH and 12 with coexisting parenchymal hemorrhages. SAH was numerically more frequent with primary thrombectomy than in the intra-arterial thrombolysis groups (14.1% vs 6.5%, P = 0.37). On multivariate analysis, independent predictors of SAH were hypertension (odds ratio = 5.39, P = 0.035), distal middle cerebral artery occlusion (odds ratio = 3.53, P = 0.027), use of rescue angioplasty after thrombectomy (odds ratio = 12.49, P = 0.004), and procedure-related vessel perforation (odds ratio = 30.72, P < 0.001). Patients with extensive SAH or coexisting parenchymal hematomas tended to have more neurologic deterioration at 3 hours (28.6% vs 0%, P = 0.11), to be less independent at discharge (modified Rankin Scale ≤ 2; 0% vs 15.4%, P = 0.5), and to experience higher mortality during hospitalization (42.9% vs 15.4%, P = 0.29). CONCLUSIONS: Procedure-related vessel perforation, rescue angioplasty after thrombectomy with MERCI devices, distal middle cerebral artery occlusion, and hypertension were independent predictors of SAH after endovascular therapy for acute ischemic stroke. Only extensive SAH or SAH accompanied by severe parenchymal hematomas may worsen clinical outcome at discharge.
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Acidente Vascular Cerebral/complicações , Hemorragia Subaracnóidea/etiologia , Trombectomia/efeitos adversos , Terapia Trombolítica/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Angioplastia , Angiografia Cerebral , Revascularização Cerebral/efeitos adversos , Etnicidade , Feminino , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Interpretação de Imagem Assistida por Computador , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/epidemiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Stents , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/cirurgia , Hemorragia Subaracnóidea/epidemiologia , Hemorragia Subaracnóidea/cirurgia , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Use of mechanical thrombectomy for acute cerebrovascular occlusions is increasing. Preintervention MRI patterns may be helpful in predicting prognosis. METHODS: We reviewed all Merci thrombectomy cases of either terminal ICA or M1 occlusions and classified them according to diffusion MRI patterns of (1) completed basal ganglia infarct (pure M1a), (2) near-completed basal ganglia infarct (incomplete M1a), and (3) relative sparing of deep MCA field (M1b). We compared the M1a and M1b patients with respect to neurological deficit on presentation, recanalization rates, hospital length of stay, and disability on discharge. We also determined whether deep MCA compromise predicted hematomal hemorrhagic transformation (HT) and whether this correlated with worse clinical outcome at discharge. RESULTS: The M1a group had worse pre-Merci NIHSS (21 versus 14, P=0.004), worse discharge NIHSS (12 versus 4, P<0.001), longer hospital length of stay (11.5 versus 6.4 days, P=0.003), and higher rates of discharge mRS > or = 3 (OR 8.4, 95% CI 2.1 to 44.7) despite equivalent recanalization rates when compared to the M1b group. The M1a group had a higher rate of parenchymal hematomal HT (OR 6.7, 95% CI 1.02 to 183.3). Patients with such hematomal HT had higher rates of death or dependency discharge (100% versus 60%, OR=infinite). CONCLUSIONS: Among patients with ICA and M1 occlusions, preintervention diffusion MRI evidence of advanced injury in the basal ganglia bodes worse dysfunction and disability at discharge, longer hospital stays, and higher rates of hemorrhage after intervention when compared to other diffusion patterns.
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Doença Cerebrovascular dos Gânglios da Base/patologia , Infarto Cerebral/patologia , Imagem de Difusão por Ressonância Magnética/métodos , Infarto da Artéria Cerebral Média/patologia , Trombose Intracraniana/patologia , Trombectomia/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Doença Cerebrovascular dos Gânglios da Base/fisiopatologia , Doença Cerebrovascular dos Gânglios da Base/cirurgia , Hemorragia Cerebral/epidemiologia , Hemorragia Cerebral/patologia , Hemorragia Cerebral/fisiopatologia , Infarto Cerebral/fisiopatologia , Infarto Cerebral/cirurgia , Feminino , Humanos , Infarto da Artéria Cerebral Média/fisiopatologia , Infarto da Artéria Cerebral Média/cirurgia , Trombose Intracraniana/fisiopatologia , Trombose Intracraniana/cirurgia , Masculino , Pessoa de Meia-Idade , Artéria Cerebral Média/patologia , Artéria Cerebral Média/fisiopatologia , Artéria Cerebral Média/cirurgia , Avaliação de Resultados em Cuidados de Saúde/métodos , Seleção de Pacientes , Hemorragia Pós-Operatória/epidemiologia , Hemorragia Pós-Operatória/patologia , Hemorragia Pós-Operatória/fisiopatologia , Valor Preditivo dos Testes , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Retrospectivos , Índice de Gravidade de Doença , Trombectomia/efeitos adversos , Trombectomia/métodosRESUMO
OBJECT: The authors report their preliminary experience using a balloon-assisted technique (BAT) in the transarterial embolization of intracranial dural arteriovenous fistulas (DAVFs). METHODS: The authors reviewed the prospectively collected data obtained in 7 consecutive patients with DAVFs in whom embolization was achieved using transarterially injected Onyx with either the venous or arterial BAT. Procedures were performed at the Division of Interventional Neuroradiology at the University of California at Los Angeles Medical Center between September 2005 and January 2008. RESULTS: Three patients presented with cortical venous reflux and 4 did not. Three patients underwent transarterial Onyx-based embolization combined with transvenous balloon protection; the balloon was inflated in the transverse sinus in 2 of these patients and in the superior sagittal sinus in the third. One of them underwent an additional transarterial Onyx embolization with arterial BAT, whereas 4 other patients were treated with arterial BAT alone. The occipital artery was temporarily occluded with the balloon in 4 of these cases, whereas in the fifth, the authors used temporary balloon occlusion of the middle meningeal artery. Angiograms obtained immediately after embolization demonstrated complete or near-complete obliteration of the fistula in 6 patients and partial occlusion in 1 patient. There were no immediate or postprocedural complications. Two patients who presented with intracranial hemorrhage never suffered a second hemorrhage, and all other patients experienced either complete resolution or significant improvement of their symptoms. CONCLUSIONS: The BAT provides a new complementary method in the transarterial embolization of DAVFs that are not amenable to transvenous embolization. The venous BAT protects the patency of critical venous pathways, whereas the arterial BAT provides better control of the Onyx-based embolization.
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Oclusão com Balão , Dura-Máter/irrigação sanguínea , Malformações Arteriovenosas Intracranianas/terapia , Idoso , Oclusão com Balão/métodos , Dimetil Sulfóxido/uso terapêutico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Polivinil/uso terapêutico , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND: Liquid embolic agents can achieve penetration of capillaries in tumors and thus may be even more effective at creating tumor necrosis than small particles. This study assesses the safety and efficacy of preoperative embolization of meningiomas with Onyx liquid embolic agent (Micro Therapeutics, Inc, Irvine, Calif) for delayed surgical resection. METHODS: Three cases of hypervascular intracranial meningiomas were treated by preoperative embolization with Onyx embolic agent using superselective catheterization of the feeding arteries from the ECA and the reflux-hold-reinjection technique. RESULTS: Meningiomas were devascularized successfully, and these patients did not present the symptoms of postembolization tumor swelling or hemorrhage before complete resection of the tumors 10 days later. Massive tumor necrosis was observed in all 3 cases of pathologic specimens, and shrinkage of tumor was seen by MRI as early as 8 days in 1 case. All patients had no recurrence of tumor at 12-month follow-up. CONCLUSION: Preoperative embolization with Onyx may be a useful tool for treatment of meningiomas. Palliative embolization treatment of nonresectable hypervascular intracranial tumors with Onyx warrants future clinical investigation.
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Dimetil Sulfóxido/uso terapêutico , Embolização Terapêutica , Neoplasias Meníngeas/terapia , Meningioma/terapia , Polivinil/uso terapêutico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Terapia NeoadjuvanteRESUMO
Non-coding RNAs (ncRNAs) are a class of functional RNAs that regulate gene expression in a post-transcriptional manner. NcRNAs include microRNAs, long non-coding RNAs and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes, including cerebral ischemic injury, neurodegeneration, neural development, and plasticity. Stroke is one of the leading causes of death and physical disability worldwide. Acute ischemic stroke (AIS) occurs when brain blood flow stops, and that stoppage results in reduced oxygen and glucose supply to cells in the brain. In this article, we review the latest progress on ncRNAs in relation to their implications in AIS, as well as their potential as diagnostic and prognostic biomarkers. We also review ncRNAs acting as possible therapeutic targets in future precision medicine. Finally, we conclude with a brief discussion of current challenges and future directions for ncRNAs studies in AIS, which may facilitate the translation of ncRNAs research into clinical practice to improve clinical outcome of AIS.
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Biomarcadores/metabolismo , RNA não Traduzido/metabolismo , Acidente Vascular Cerebral/patologia , Barreira Hematoencefálica/metabolismo , Isquemia Encefálica/genética , Isquemia Encefálica/patologia , Humanos , Microglia/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo/genética , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genéticaRESUMO
BACKGROUND AND PURPOSE: The impact of blood-brain barrier (BBB) disruption can be detected by intraparenchymal hyperdense lesion on the computed tomography (CT) scan after endovascular stroke therapy. The purpose of this study was to determine whether early BBB disruption predicts intracranial hemorrhage and poor outcome in patients with acute ischemic stroke treated with mechanical thrombectomy. METHODS: We analyzed patients with anterior circulation stroke treated with mechanical thrombectomy and identified BBB disruption on the noncontrast CT images immediately after endovascular treatment. Follow-up CT or magnetic resonance imaging scan was performed at 24 hours to assess intracranial hemorrhage. We dichotomized patients into those with moderate BBB disruption versus those with minor BBB disruption and no BBB disruption. We evaluated the association of moderate BBB disruption after mechanical thrombectomy with intracranial hemorrhage and clinical outcomes. RESULTS: Moderate BBB disruption after mechanical thrombectomy was found in 56 of 210 patients (26.7%). Moderate BBB disruption was independently associated with higher rates of hemorrhagic transformation (OR 25.33; 95% CI 9.93-64.65; P < .001), parenchymal hematoma (OR 20.57; 95% CI 5.64-74.99; P < .001), and poor outcome at discharge (OR 2.35; 95% CI 1.09-5.07; P = .03). The association of BBB disruption with intracranial hemorrhage remained in patients with successful reperfusion after mechanical thrombectomy. The location of BBB disruption was not associated with intracranial hemorrhage and poor outcome. CONCLUSIONS: Moderate BBB disruption is common after mechanical thrombectomy in a quarter of patients with acute ischemic stroke and increases the risk of intracranial hemorrhage and poor outcome.
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Barreira Hematoencefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia , Hemorragia Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Barreira Hematoencefálica/lesões , Isquemia Encefálica/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Severe hemorrhagic transformation (HT) after mechanical thrombectomy predicts a poor clinical outcome in acute ischemic stroke. To better understand the mechanism of HT, we investigated the role of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) in HT after reperfusion during acute stroke and whether NOX2/4 inhibitor VAS2870 reduces reperfusion-induced HT after mechanical recanalization. METHODS: A model of reperfusion-induced HT was established in rats (n=182) with hyperglycemic challenge and 5â h middle cerebral artery occlusion followed by 19â h reperfusion. NOX inhibitor VAS2870 was delivered intravenously 30â min before reperfusion. Infarct volume, brain water content, HT, neurological score, mortality rate, blood-brain barrier (BBB) damage, neuronal apoptosis, and reactive oxygen species were determined at 24â h after cerebral ischemia. The expressions of NOX1, NOX2, NOX4, and BBB-associated proteins were measured. RESULTS: NOX2 and NOX4 upregulation and severe HT were observed in hyperglycemic rats after cerebral ischemia/reperfusion. VAS2870 suppressed oxidative stress, neuronal apoptosis, and NOX2/4 upregulation in the ischemic hemisphere. VAS2870 reduced infarct volume (17.2±5.3% vs 37.4±9.2%, p<0.01) and the frequency of reperfusion-induced parenchymal hematoma (29.7% vs 59.5%, p<0.05) at 24â h after ischemia compared with the ischemia/reperfusion group. VAS2870 attenuated brain edema and reduced reperfusion-induced BBB breakdown, resulting in improved neurological outcome (neurological deficit score 1.43±0.50 vs 2.43±0.93, p<0.001) and reduced mortality (11.9% vs 64.1%, p<0.001). CONCLUSIONS: NOX2 and NOX4 may mediate HT in rats with large vessel stroke after mechanical reperfusion. Infusion of NOX inhibitor VAS2870 before mechanical thrombectomy represents a novel adjunctive therapeutic strategy to prevent reperfusion-induced HT and improve outcome of acute stroke treatment.
Assuntos
Benzoxazóis/uso terapêutico , Isquemia Encefálica/cirurgia , Hemorragia Cerebral/tratamento farmacológico , NADPH Oxidases/antagonistas & inibidores , Traumatismo por Reperfusão/tratamento farmacológico , Reperfusão/métodos , Triazóis/uso terapêutico , Animais , Benzoxazóis/farmacologia , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patologia , Hemorragia Cerebral/metabolismo , Hemorragia Cerebral/patologia , Masculino , NADPH Oxidases/metabolismo , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Reperfusão/efeitos adversos , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Trombectomia/efeitos adversos , Trombectomia/métodos , Resultado do Tratamento , Triazóis/farmacologiaRESUMO
BACKGROUND: Inhibition of the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (NOX) pathway improves the neurological outcome in the transient middle cerebral artery occlusion (tMCAO) animal model. In this study we analyzed the microRNAs profile targeting NOX2 and NOX4 genes and its response to NOX2/4 inhibitor VAS2870 to understand the mechanisms of this protective effect. METHODS: The intraluminal filament tMCAO model was established in hyperglycemic rats (n=106) with 5â hours ischemia followed by 19â hours reperfusion. NOX inhibitor VAS2870 was delivered intravenously before reperfusion. Infarct volume, hemorrhagic transformation, and mortality were determined at 24â hours after cerebral ischemia. MicroRNAs profile targeting NOX2 and NOX4 genes were predicted by microRNA databases and further evaluated by microRNA microarray and quantitative RT-PCR. RESULTS: Ten microRNAs potentially targeting NOX2 and NOX4 genes (including microRNA-29a, microRNA-29c, microRNA-126a, microRNA-132, microRNA-136, microRNA-138, microRNA-139, microRNA-153, microRNA-337, and microRNA-376a) were significantly downregulated in the ischemic hemisphere in the tMCAO group compared with the sham-operated group, as shown by microRNA microarray and quantitative RT-PCR (all p<0.05). Intravenous treatment with NOX inhibitor VAS2870 before reperfusion increased the expression of microRNA-29a, microRNA-29c, microRNA-126a, and microRNA-132 compared with the tMCAO group (all p<0.05). CONCLUSIONS: Several microRNAs potentially targeting NOX2 and NOX4 genes displayed altered levels in hyperglycemic rats with the tMCAO model, suggesting their regulatory roles and targeting potentials for acute ischemic stroke treatment. Targeting specific microRNAs may represent a novel intervention opportunity to improve outcome and reduce hemorrhagic transformation after mechanical reperfusion for acute ischemic stroke.
Assuntos
Benzoxazóis/farmacologia , Infarto da Artéria Cerebral Média/enzimologia , MicroRNAs/fisiologia , NADPH Oxidases/antagonistas & inibidores , NADPH Oxidases/metabolismo , Reperfusão/métodos , Triazóis/farmacologia , Animais , Benzoxazóis/uso terapêutico , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/enzimologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Masculino , Ratos , Ratos Sprague-Dawley , Resultado do Tratamento , Triazóis/uso terapêuticoRESUMO
BACKGROUND: The influence of cerebral microbleeds (CMBs) on post-thrombolytic hemorrhagic transformation (HT) in patients with acute ischemic stroke remains controversial. OBJECTIVE: To investigate the association of CMBs with HT and clinical outcomes among patients with large-vessel occlusion strokes treated with mechanical thrombectomy. METHODS: We analyzed patients with acute stroke treated with Merci Retriever, Penumbra system or stent-retriever devices. CMBs were identified on pretreatment T2-weighted, gradient-recall echo MRI. We analyzed the association of the presence, burden, and distribution of CMBs with HT, procedural complications, in-hospital mortality, and clinical outcome. RESULTS: CMBs were detected in 37 (18.0%) of 206 patients. Seventy-three foci of microbleeds were identified. Fourteen patients (6.8%) had ≥2 CMBs, only 1 patient had ≥5 CMBs. Strictly lobar CMBs were found in 12 patients, strictly deep CMBs in 12 patients, strictly infratentorial CMBs in 2 patients, and mixed CMBs in 11 patients. There were no significant differences between patients with CMBs and those without CMBs in the rates of overall HT (37.8% vs 45.6%), parenchymal hematoma (16.2% vs 19.5%), procedure-related vessel perforation (5.4% vs 7.1%), in-hospital mortality (16.2% vs 18.3%), and modified Rankin Scale score 0-3 at discharge. CMBs were not independently associated with HT or in-hospital mortality in patients treated with either thrombectomy or intravenous thrombolysis followed by thrombectomy. CONCLUSIONS: Patients with CMBs are not at increased risk for HT and mortality following mechanical thrombectomy for acute stroke. Excluding such patients from mechanical thrombectomy is unwarranted. The risk of HT in patients with ≥5 CMBs requires further study.
Assuntos
Isquemia Encefálica/terapia , Transtornos Cerebrovasculares , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/mortalidade , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/etiologia , Hemorragia Cerebral/mortalidade , Transtornos Cerebrovasculares/complicações , Transtornos Cerebrovasculares/diagnóstico por imagem , Transtornos Cerebrovasculares/terapia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Trombectomia/efeitos adversosRESUMO
The interval appearance of cerebral microbleeds (CMBs) after endovascular treatment has never been described. We investigated the frequency and predictors of new CMBs that developed shortly after mechanical thrombectomy for acute ischemic stroke, and its impact on clinical outcome.We retrospectively analyzed patients with large-vessel occlusion strokes treated with Merci Retriever, Penumbra System, or stent-retriever devices. Serial T2*-weighted gradient-recall echo (GRE) magnetic resonance imaging (MRI) before and 48 h after endovascular thrombectomy were assessed to identify new CMBs. We examined independent factors associated with new CMBs after mechanical thrombectomy. We analyzed the association of the presence, burden, and distribution of new CMBs with clinical outcome.A total of 187 consecutive patients with serial GRE were enrolled in this study. CMBs were evident in 36 (19.3%) patients before mechanical thrombectomy. New CMBs occurred in 41 (21.9%) patients after mechanical thrombectomy. Of the 68 new CMBs, 45 appeared in the lobar location, 18 in the deep location and 5 in the infratentorial location. The presence of baseline CMBs was associated with new CMBs after mechanical thrombectomy (OR 5.38; 95% CI 2.13-13.59; P < 0.001), no matter whether the patients were treated primarily with mechanical thrombectomy or with intravenous thrombolysis followed by mechanical thrombectomy. Patients with new CMBs did not have increased rates of hemorrhagic transformation, in-hospital mortality, and modified Rankin Scale score 4 to 6 at discharge.New CMBs are common after mechanical thrombectomy in one-fifth of patients with acute ischemic stroke. Baseline CMBs before mechanical thrombectomy predicts the development of new CMBs. New CMBs after mechanical thrombectomy do not influence clinical outcome.
Assuntos
Encéfalo/irrigação sanguínea , Hemorragia/etiologia , Microcirculação , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Trombectomia/métodosRESUMO
BACKGROUND: A swine model of carotid atherosclerosis may greatly facilitate the identification of imaging characteristics of vulnerable plaques and the preclinical evaluation of endovascular intervention. In this study we assess the association of matrix metalloproteinase (MMP)-9 expression and neovascularity in carotid atherosclerotic plaques with MRI patterns in a swine model. METHODS: Carotid atherosclerosis models were created in miniswine using a combination of partial ligation and a high cholesterol diet. The animals were imaged in a 1.5 T MR scanner at 3 months and carotid arteries were obtained for histopathological and immunohistochemical examination. Contrast-enhanced T1-weighted imaging (T1WI) was used to match the histology findings. The contrast-to-noise ratio (CNR) of the plaques on T1WI and contrast-enhanced T1WI were measured and the association of MMP-9 expression and neovascularity in the carotid plaque with CNR on MRI was analyzed. RESULT: Forty carotid artery segments were matched between MRI and histology. All segments were advanced carotid atherosclerotic plaques. The matched contrast-enhanced T1WI and histology slices showed good correlation for ratio of plaque size to lumen diameter (r=0.94, p<0.001). Plaque CNR on contrast-enhanced T1WI was higher in plaques with strong MMP-9 expression than in those with weak MMP-9 expression (p=0.05). Plaque CNR on contrast-enhanced T1WI was also higher in plaques with marked neovascularization than in those without (p=0.02). CONCLUSIONS: Increased plaque CNR on contrast-enhanced T1WI is associated with MMP-9 expression and neovascularization in carotid atherosclerotic plaques and may be used to identify vulnerable plaques.
Assuntos
Doenças das Artérias Carótidas/enzimologia , Modelos Animais de Doenças , Regulação Enzimológica da Expressão Gênica , Imageamento por Ressonância Magnética/métodos , Metaloproteinase 9 da Matriz/biossíntese , Placa Aterosclerótica/enzimologia , Animais , Doenças das Artérias Carótidas/diagnóstico , Meios de Contraste , Placa Aterosclerótica/diagnóstico , Suínos , Porco MiniaturaRESUMO
OBJECTIVE: Carotid intraplaque hemorrhage may result in rapid worsening of stenosis and thrombus formation leading to stroke in patients with carotid atherosclerosis. The purpose of this study was to assess the association of the lesional expression of matrix metalloproteinase (MMP)-9 with carotid plaque and intraplaque hemorrhage in a swine model. METHODS: Carotid atherosclerosis was induced in miniswine using a combination of partial ligation and a high cholesterol diet. The carotid artery and rete mirabile were obtained for histopathological and immunohistochemical studies at 3 months. Atherosclerotic changes were classified by Stary stage according to the American Heart Association and the features of vulnerable carotid plaque were assessed. The association of MMP-9 expression in the carotid plaque with intraplaque hemorrhage was analyzed. RESULTS: One hundred and ninety-one carotid segments from 10 carotid artery models were assessed. Among 139 segments with atherosclerotic changes, 102 had advanced plaque (Stary stage IV-VI). Atheroemboli were found in all 10 rete mirabili, confirming the presence of vulnerable ipsilateral carotid plaques. There was a trend to increased MMP-9 expression in the group with advanced plaque. Areas positive for MMP-9 were significantly greater in plaques with intraplaque hemorrhage than in those without intraplaque hemorrhage (11.84±1.22% vs 6.63±0.59%, p<0.001). CONCLUSIONS: Increased expression of MMP-9 is associated with intraplaque hemorrhage in a swine model of vulnerable carotid atherosclerosis.
Assuntos
Doenças das Artérias Carótidas/enzimologia , Hemorragia/enzimologia , Metaloproteinase 8 da Matriz/biossíntese , Placa Aterosclerótica/complicações , Placa Aterosclerótica/enzimologia , Animais , Artérias Carótidas/patologia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/patologia , Estenose das Carótidas/patologia , Hemorragia/etiologia , Hemorragia/patologia , Imuno-Histoquímica , Embolia Intracraniana/patologia , Inclusão em Parafina , Suínos , Porco MiniaturaRESUMO
OBJECTIVES: Experience of flow control techniques during endovascular treatment of intracranial dural arteriovenous fistulas (DAVFs) using the Onyx liquid embolic system is reported, with an emphasis on high flow shunts. METHODS: Data were evaluated in patients with DAVFs treated endovascularly with Onyx. Adjunctive techniques with coils, acrylics and balloon assistance were utilized to reduce the rate of flow with transarterial and transvenous approaches. RESULTS: The following types of adjunctive techniques were used in 58 patients who underwent a total of 84 embolization sessions with Onyx: transvenous coiling with transvenous or transarterial Onyx embolization in 36 patients, transarterial coiling with transarterial Onyx embolization in eight patients, arterial or venous balloon assisted technique with transarterial or transvenous Onyx embolization in 11 patients, transarterial high concentration acrylics with transarterial Onyx embolization in one patient and staged transarterial or transvenous coiling and Onyx embolization in two patients. Complete obliteration of the fistulae was achieved in 41 patients (70.7%) and 27 patients (65.9%) with high flow fistulae after endovascular treatment alone. Periprocedural complications were encountered in 16 patients, and 13 complications were associated with the adjunctive techniques. There were four neurologic and two non-neurologic clinical sequelae. Distal Onyx migration occurred in four, microcatheter retention in three and cranial neuropathy in three patients. There was one instance each of cerebellar hemorrhage, thromboembolism, coil stretching and retention, and dissection. 56 survivors experienced complete resolution or significant improvement of their symptoms on follow-up. CONCLUSIONS: Flow control techniques are safe and effective adjunctive methods in primary endovascular Onyx embolization of high flow DAVFs.