Thrombectomy for Stroke in the Public Health Care System of Brazil.

BACKGROUND: Randomized trials involving patients with stroke have established that outcomes are improved with the use of thrombectomy for large-vessel occlusion. These trials were performed in high-resource countries and have had limited effects on medical practice in low- and middle-income countries. METHODS: We studied the safety and efficacy of thrombectomy in the public health system of Brazil. In 12 public hospitals, patients with a proximal intracranial occlusion in the anterior circulation that could be treated within 8 hours after the onset of stroke symptoms were randomly assigned in a 1:1 ratio to receive standard care plus mechanical thrombectomy (thrombectomy group) or standard care alone (control group). The primary outcome was the score on the modified Rankin scale (range, 0 [no symptoms] to 6 [death]) at 90 days. RESULTS: A total of 300 patients were enrolled, including 79 who had undergone thrombectomy during an open-label roll-in period. Approximately 70% in the two groups received intravenous alteplase. The trial was stopped early because of efficacy when 221 of a planned 690 patients had undergone randomization (111 to the thrombectomy group and 110 to the control group). The common odds ratio for a better distribution of scores on the modified Rankin scale at 90 days was 2.28 (95% confidence interval [CI], 1.41 to 3.69; P = 0.001), favoring thrombectomy. The percentage of patients with a score on the modified Rankin scale of 0 to 2, signifying an absence of or minor neurologic deficit, was 35.1% in the thrombectomy group and 20.0% in the control group (difference, 15.1 percentage points; 95% CI, 2.6 to 27.6). Asymptomatic intracranial hemorrhage occurred in 51.4% of the patients in the thrombectomy group and 24.5% of those in the control group; symptomatic intracranial hemorrhage occurred in 4.5% of the patients in each group. CONCLUSIONS: In this randomized trial conducted in the public health care system of Brazil, endovascular treatment within 8 hours after the onset of stroke symptoms in conjunction with standard care resulted in better functional outcomes at 90 days than standard care alone. (Funded by the Brazilian Ministry of Health; RESILIENT ClinicalTrials.gov number, NCT02216643.).

Experience on Mechanical Thrombectomy for Acute Stroke Treatment in a Brazilian University Hospital.

BACKGROUND: Brazil is a developing country struggling to reduce its extreme social inequality, which is reflected on shortage of health-care infrastructure, mainly to the low-income class, which depends exclusively on the public health system. In Brazil, less than 1% of stroke patients have access to intravenous thrombolysis in a stroke unit, and constraints to the development of mechanical thrombectomy in the public health system increase the social burden of stroke. OBJECTIVE: Report the feasibility of mechanical thrombectomy as part of routine stroke care in a Brazilian public university hospital. METHODS: Prospective data were collected from all patients treated for acute ischemic stroke with mechanical thrombectomy from June 2011 to March 2016. Combined thrombectomy was performed in eligible patients for intravenous thrombolysis if they presented occlusion of large artery. For those patients ineligible for intravenous thrombolysis, primary thrombectomy was performed as long as there was no evidence of significant ischemia for anterior circulation stroke (Alberta Stroke Program Early CT score >6) within a 6-hour time window, and also for those patients with wake-up stroke or posterior circulation stroke, regardless of the time of symptoms onset. RESULTS: A total of 161 patients were evaluated, resulting in an overall successful recanalization rate of 76% and symptomatic intracranial hemorrhage rate of 6.8%. At 3 months, 36% of the patients had modified Rankin Scale score less than or equal to 2. The overall mortality rate was 23%. CONCLUSION: Our study, the first ever large series of mechanical thrombectomy in Brazil, demonstrates acceptable efficacy and safety results, even under restricted conditions outside the ideal scenario of trial studies.

Sonic Hedgehog mutations are not a common cause of congenital hypopituitarism in the absence of complex midline cerebral defects.

CONTEXT AND OBJECTIVE: Sonic Hedgehog (SHH) and GLI2, an obligatory mediator of SHH signal transduction, are holoprosencephaly (HPE)-associated genes essential in pituitary formation. GLI2 variants have been found in patients with congenital hypopituitarism without complex midline cerebral defects (MCD). However, data on the occurrence of SHH mutations in these patients are limited. We screened for SHH and GLI2 mutations or copy number variations (CNV) in patients with congenital hypopituitarism without MCD or with variable degrees of MCD. PATIENTS AND METHODS: Detailed data on clinical, laboratory and neuroimaging findings of 115 patients presenting with congenital hypopituitarism without MCD, septo-optic dysplasia or HPE were analysed. The SHH and GLI2 genes were directly sequenced, and the presence of gene CNV was analysed by multiplex ligation-dependent probe amplification (MLPA). RESULTS: Anterior pituitary deficiency was found in 74% and 53% of patients with SOD or HPE, respectively. Diabetes insipidus was common in patients with HPE (47%) but infrequent in patients with congenital hypopituitarism or SOD (7% and 8%, respectively). A single heterozygous nonsense SHH mutation (p.Tyr175Ter) was found in a patient presenting with hypopituitarism and alobar HPE. No other SHH mutations or CNV were found. Nine GLI2 variations (8 missense and 1 frameshift) including a homozygous and a compound heterozygous variation were found in patients with congenital hypopituitarism or SOD, but not in HPE patients. No GLI2 CNV were found. CONCLUSION: SHH mutations or copy number variations are not a common cause of congenital hypopituitarism in patients without complex midline cerebral defects. GLI2 variants are found in some patients with congenital hypopituitarism without complex midline cerebral defects or septo-optic dysplasia. However, functional analyses of these variants are needed to strengthen genotype-phenotype relationship.

Early versus late carotid artery stenting for symptomatic carotid stenosis.

INTRODUCTION: Early carotid revascularization (≤ 14 days) is recommended for symptomatic carotid stenosis. Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA); however, safety data on early CAS is controversial. The study aims to compare early versus late CAS, when CAS is performed as a first intention revascularization strategy. METHODS: A retrospective analysis of all symptomatic patients admitted to our stroke unit who underwent CAS was conducted. Patients were divided between two groups: patients who had undergone CAS within 14 days after symptoms and those who had undergone CAS later. Primary endpoints were ipsilateral ischemic stroke or ipsilateral parenchymal hemorrhage (iPH) at 30 days. The secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) at the 30-day and at the 12-month follow-up. RESULTS: One hundred twenty-seven consecutive patients were evaluated. Primary endpoints obtained in the early and late CAS groups were, respectively, ipsilateral stroke (2.0% vs. 2.6%, P = 1.00) and iPH (2.0% vs. 0.0%, P = 0.40). The rates of MACCE between the early and the late CAS groups were, respectively, (7.8% vs. 2.6%, P = 0.21) at the 30-day follow-up, and (12.2% vs. 10.5%, P = 0.77) at the 12-month follow-up. CONCLUSIONS: In this study, CAS seems to be safe when used as first intention revascularization treatment within 2 weeks of symptoms, if infarcted area is less than one third of the middle cerebral artery territory. Our results need to be confirmed by larger studies.

Thrombectomy for Anterior Circulation Stroke in a Witnessed Late Time Window Versus Early Time Window.

Introduction: Thrombectomy is the standard treatment for anterior circulation stroke due to large vessel occlusions in a late time window (6 to 24 hours) for patients selected based on perfusion imaging. Most patients treated in late time window studies presented as unwitnessed or wake-up strokes. Whether patients presenting with unwitnessed stroke have an actual time window greater than 6 hours is unclear. The aim of this study was to assess the outcomes of thrombectomy in the treatment of patients presenting with anterior circulation large vessel stroke in an actual late time window of more than 6 hours. Methods: This single-center registry of thrombectomy in the treatment of stroke caused by anterior circulation large vessel occlusions (LVOs) included 430 patients treated between 2011 and 2019. Patients were divided into 2 groups: an early time window (≤ 6 hours) group and a late time window group (> 6 hours). Results: Outcomes of the early and the late time window groups, respectively, were recanalization of 86.8% vs 82.7% (P = .29), symptomatic intracranial hemorrhage of 8.2% vs 5.7% (P = .40), good clinical outcome of 45.4% vs 41.3% (P = .46), and mortality of 20.2% vs 25% (P = .30) at 3 months. Conclusions: Thrombectomy for anterior circulation large vessel occlusions after 6 hours of symptoms onset seems to be as safe and effective as the standard thrombectomy within 6 hours from symptoms onset, even without perfusion analysis. Randomized trials are needed to confirm these findings.

Endovascular treatment of aneurysm arising from fenestration of the supraclinoid internal carotid artery--two case reports.

We report two cases of aneurysm located in a fenestration of the supraclinoid internal carotid artery, an extremely rare anatomical variant, and describe the feasibility of endovascular treatment using two different strategies applicable for each case. Each presented aneurysm had a particular location on the fenestration, which led to different endovascular approaches. In one case, the aneurysm arose from the proximal junction of fenestration, involving both of its limbs. For this aneurysm, the treatment strategy adopted aimed to achieve a selective exclusion. In the second case, two aneurysms arose from the minor limb of the fenestration, which could be entirely excluded, considering the absence of perforating arteries arising from that carotid segment. To our knowledge, these two cases are the first ICA fenestration aneurysms treated exclusively by endovascular approach, showing two treatment strategies using coils in association to two different endovascular devices (stent/TrisPan(®)).

Treatment of ruptured intra-cranial internal carotid artery dissection using a flow-diverter stent.

In the presence of associated subarachnoid hemorrhage, the treatment of arterial dissection can be classified as either deconstructive (involving occlusion or sacrifice of the parent vessel) or reconstructive (preserving blood-flow through the parent vessel). In both treatment strategies, the main goal is to prevent any further risk of rebleeding. However, reconstructive treatment is reserved only for those patients in whom occlusion of the parent vessel is not feasible due to an insufficient collateral supply. This report is of a case of intra-cranial carotid artery dissection treated by a reconstructive endovascular approach, with deployment of a flow-diverter stent, for the management of an associated subarachnoid hemorrhage. This is, to the authors' knowledge, the first report of the use of a flow-diverter device as the main treatment of a ruptured supraclinoid carotid artery dissection.

Performance evolution over 645 acute stroke thrombectomies in a public Brazilian healthcare institution.

BACKGROUND: Assessment of the impact of the thrombectomy learning curve on clinical outcomes is essential for developing healthcare system protocols. AIMS: The aim of this study was to assess the effect of thrombectomy case volume on procedural and clinical outcomes in a Brazilian registry. METHODS: A total of 645 patients with acute ischemic stroke treated by thrombectomy were included in the analysis. Patients were divided into two groups regarding the period of treatment: the early period group and the late period group. RESULTS: In the adjusted analysis, treatment in the late period was an independent predictor of recanalization (odds ratio 1.91, 95% CI 1.28-2.86) and excellent neurologic outcomes at three months (odds ratio 1.77, 95% CI 1.04-3.01). Treatment in the late period had no significant association with mortality (odds ratio 0.88, 95% CI 0.55-1.41). CONCLUSIONS: An increase in thrombectomy case volume for the treatment of AIS over time was an independent predictor of recanalization and excellent neurologic outcome.

Carotid artery stenting in the context of endovascular treatment of acute ischemic stroke.

UNLABELLED: Mechanical thrombectomy as an adjunctive to intravenous thrombolysis is now the standard treatment for acute ischemic stroke (AIS) due to large vessel occlusions. However, the best management of acute carotid tandem occlusions (CTO) remains controversial. METHOD: Twenty patients underwent endovascular treatment of acute CTO. The primary endpoint was the composite rate of complete or partial recanalization without a symptomatic intracranial hemorrhage (sICH). Secondary endpoints were recanalization times, procedure times, and clinical outcomes at three months. RESULTS: The primary endpoint was reached in 17 (85%) patients. Recanalization rate was reached in 90% of patients (19/20) and sICH rate was 5% (1/20). At the 3-month follow-up we obtained a mRS ≤ 2 rate of 35% (7/20) and a mortality rate of 20% (4/20). CONCLUSION: Carotid angioplasty stenting and endovascular treatment of AIS due to CTO appears effective with an acceptable rate of sICH.

A comparison between magnetic resonance angiography at 3 Teslas (time-of-flight and contrast-enhanced) and flat-panel digital subtraction angiography in the assessment of embolized brain aneurysms.

PURPOSE: To compare the time-of-flight and contrast-enhanced- magnetic resonance angiography techniques in a 3 Tesla magnetic resonance unit with digital subtraction angiography with the latest flat-panel technology and 3D reconstruction in the evaluation of embolized cerebral aneurysms. INTRODUCTION: Many embolized aneurysms are subject to a recurrence of intra-aneurismal filling. Traditionally, imaging surveillance of coiled aneurysms has consisted of repeated digital subtraction angiography. However, this method has a small but significant risk of neurological complications, and many authors have advocated the use of noninvasive imaging methods for the surveillance of embolized aneurysms. METHODS: Forty-three aneurysms in 30 patients were studied consecutively between November 2009 and May 2010. Two interventional neuroradiologists rated the time-of-flight-magnetic resonance angiography, the contrast-enhanced-magnetic resonance angiography, and finally the digital subtraction angiography, first independently and then in consensus. The status of aneurysm occlusion was assessed according to the Raymond scale, which indicates the level of recanalization according to degrees: Class 1: excluded aneurysm; Class 2: persistence of a residual neck; Class 3: persistence of a residual aneurysm. The agreement among the analyses was assessed by applying the Kappa statistic. RESULTS: Inter-observer agreement was excellent for both methods (K = 0.93; 95 % CI: 0.84-1). Inter-technical agreement was almost perfect between time-of-flight-magnetic resonance angiography and digital subtraction angiography (K = 0.98; 95 % CI: 0.93-1) and between time-of-flight-magnetic resonance angiography and contrast-enhanced-magnetic resonance angiography (K = 0.98; 95% CI: 0.93-1). Disagreement occurred in only one case (2.3%), which was classified as Class I by time-of-flight-magnetic resonance angiography and Class II by digital subtraction angiography. The agreement between contrast-enhanced-magnetic resonance angiography and digital subtraction angiography was perfect (K = 1; 95% CI: 1-1). In three patients, in-stent stenosis was identified by magnetic resonance angiography but not confirmed by digital subtraction angiography. CONCLUSION: Digital subtraction angiography and both 3T magnetic resonance angiography techniques have excellent reproducibility for the assessment of aneurysms embolized exclusively with coils. In those cases also treated with stent remodeling, digital subtraction angiography may still be necessary to confirm eventual parent artery stenosis, as identified by magnetic resonance angiography.

Carotid artery stenting in the context of endovascular treatment of acute ischemic stroke / Angioplastia com stent de carótida no contexto do tratamento endovascular do acidente vascular cerebral isquêmico agudo

ABSTRACT Mechanical thrombectomy as an adjunctive to intravenous thrombolysis is now the standard treatment for acute ischemic stroke (AIS) due to large vessel occlusions. However, the best management of acute carotid tandem occlusions (CTO) remains controversial. Method Twenty patients underwent endovascular treatment of acute CTO. The primary endpoint was the composite rate of complete or partial recanalization without a symptomatic intracranial hemorrhage (sICH). Secondary endpoints were recanalization times, procedure times, and clinical outcomes at three months. Results The primary endpoint was reached in 17 (85%) patients. Recanalization rate was reached in 90% of patients (19/20) and sICH rate was 5% (1/20). At the 3-month follow-up we obtained a mRS ≤ 2 rate of 35% (7/20) and a mortality rate of 20% (4/20). Conclusion Carotid angioplasty stenting and endovascular treatment of AIS due to CTO appears effective with an acceptable rate of sICH.

RESUMO Trombectomia mecânica com stentrievers associada a trombólise endovenosa com rTPA é o tratamento padrão-ouro do acidente vascular cerebral isquêmico agudo (AVCi) devido à oclusões de grandes vasos. No entanto, a melhor estratégia terapêutica para oclusões carotídeas combinadas ainda permanece controversa. Método Vinte paciente receberam tratamento endovascular. O desfecho primário foi a taxa de recanalização completa sem sangramento intracraniano sintomático. Os desfechos secundários foram os tempos de recanalização, duração dos procedimentos e desfechos clínicos em 3 meses. Resultados O desfecho primário foi alcançado em 17 (85%) pacientes. A taxa de recanalização foi de 90% (19/20) e a taxa de HIS foi de 5% (1/20). Em três meses, foi obtido bom desfecho neurológico em 35% (7/20) dos pacientes e a mortalidade foi de 20% (4/20). Conclusão A angioplastia com stent de carotída associada ao tratamento endovascular para oclusões combinadas agudas de carótida parece ser efetiva sem um aumento de HIS.

Endovascular therapy for selected (most non-surgical) intracranial aneurysms in a Brazilian University Hospital.

OBJECTIVE: The objective of this study was to evaluate technical, clinical and angiographic results of a nonsurgical series of intracranial aneurysms treated by endovascular approach at Hospital das Clínicas of Medical School of Ribeirão Preto - University of São Paulo. METHOD: Between August 2005 and November 2008, 137 aneurysms in 106 patients were endovascularly treated. Of these, 101 were unruptured in 75 patients and 36 aneurysms in 31 patients were treated during the acute phase. The data were prospectively studied. RESULTS: Sixty three aneurysms (46%) were treated with coils alone, 52 (38%) with balloon remodeling, 15 (10.9%) with stent remodeling, and 7 (5.1%) with therapeutic occlusion of the internal carotid artery. Six clinical complications (5.7%) were related to the procedures, 3 (2.8%) transitory and 3 (2.8%) permanent. Angiographic follow-up was available for 97 aneurysms (70.8%), clinical monitoring for 77 patients (72.6%) and telephone contact for 97 (91.5%). CONCLUSION: The technical, clinical and angiographic results found in this study are similar to those reported in the literature.

A comparison between magnetic resonance angiography at 3 teslas (time-of-flight and contrast-enhanced) and flat-panel digital subtraction angiography in the assessment of embolized brain aneurysms

PURPOSE: To compare the time-of-flight and contrast-enhanced- magnetic resonance angiography techniques in a 3 Tesla magnetic resonance unit with digital subtraction angiography with the latest flat-panel technology and 3D reconstruction in the evaluation of embolized cerebral aneurysms. INTRODUCTION: Many embolized aneurysms are subject to a recurrence of intra-aneurismal filling. Traditionally, imaging surveillance of coiled aneurysms has consisted of repeated digital subtraction angiography. However, this method has a small but significant risk of neurological complications, and many authors have advocated the use of noninvasive imaging methods for the surveillance of embolized aneurysms. METHODS: Forty-three aneurysms in 30 patients were studied consecutively between November 2009 and May 2010. Two interventional neuroradiologists rated the time-of-flight-magnetic resonance angiography, the contrast-enhanced-magnetic resonance angiography, and finally the digital subtraction angiography, first independently and then in consensus. The status of aneurysm occlusion was assessed according to the Raymond scale, which indicates the level of recanalization according to degrees: Class 1: excluded aneurysm; Class 2: persistence of a residual neck; Class 3: persistence of a residual aneurysm. The agreement among the analyses was assessed by applying the Kappa statistic. RESULTS: Inter-observer agreement was excellent for both methods (K = 0.93; 95 percent CI: 0.84-1). Inter-technical agreement was almost perfect between time-of-flight-magnetic resonance angiography and digital subtraction angiography (K = 0.98; 95 percent CI: 0.93-1) and between time-of-flight-magnetic resonance angiography and contrast-enhanced-magnetic resonance angiography (K = 0.98; 95 percent CI: 0.93-1). Disagreement occurred in only one case (2.3 percent), which was classified as Class I by time-of-flight-magnetic resonance angiography and Class II by digital subtraction angiography. The agreement between contrast-enhanced-magnetic resonance angiography and digital subtraction angiography was perfect (K = 1; 95 percent CI: 1-1). In three patients, in-stent stenosis was identified by magnetic resonance angiography but not confirmed by digital subtraction angiography. CONCLUSION: Digital subtraction angiography and both 3T magnetic resonance angiography techniques have excellent reproducibility for the assessment of aneurysms embolized exclusively with coils. In those cases also treated with stent remodeling, digital subtraction angiography may still be necessary to confirm eventual parent artery stenosis, as identified by magnetic resonance angiography.

Endovascular therapy for selected (most non-surgical) intracranial aneurysms in a Brazilian University Hospital / Tratamento endovascular de aneurismas selecionados (maioria não cirúrgicos) em um hospital universitário brasileiro

OBJECTIVE: The objective of this study was to evaluate technical, clinical and angiographic results of a nonsurgical series of intracranial aneurysms treated by endovascular approach at Hospital das Clínicas of Medical School of Ribeirão Preto - University of São Paulo. METHOD: Between August 2005 and November 2008, 137 aneurysms in 106 patients were endovascularly treated. Of these, 101 were unruptured in 75 patients and 36 aneurysms in 31 patients were treated during the acute phase. The data were prospectively studied. RESULTS: Sixty three aneurysms (46 percent) were treated with coils alone, 52 (38 percent) with balloon remodeling, 15 (10.9 percent) with stent remodeling, and 7 (5.1 percent) with therapeutic occlusion of the internal carotid artery. Six clinical complications (5.7 percent) were related to the procedures, 3 (2.8 percent) transitory and 3 (2.8 percent) permanent. Angiographic follow-up was available for 97 aneurysms (70.8 percent), clinical monitoring for 77 patients (72.6 percent) and telephone contact for 97 (91.5 percent). CONCLUSION: The technical, clinical and angiographic results found in this study are similar to those reported in the literature.

OBJETIVO: Nosso objetivo foi avaliar os resultados técnicos, clínicos e angiográficos de uma série de aneurismas intracranianos não cirúrgicos tratados por via endovascular no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto da Universidade de São Paulo e comparar com os dados disponíveis na literatura atualmente. MÉTODO: Entre agosto de 2005 e novembro de 2008, 137 aneurismas foram tratados por via endovascular em 106 pacientes. Destes, 101 eram não rotos em 75 pacientes e 36 aneurismas foram tratados em 31 pacientes durante a fase aguda de ruptura. Os dados foram incluídos de maneira prospectiva. RESULTADOS: Sessenta e três aneurismas (46 por cento) foram tratados com técnica simples, 52 (38 por cento) com remodelagem por balão, 15 (10,9 por cento) com remodelagem por stent e 7 (5,1 por cento) por oclusão terapêutica da carótida interna. Seis complicações clínicas ocorreram (5,7 por cento), 3 (2,8 por cento) transitórias e 3 (2,8 por cento) permanentes. Seguimento angiográfico foi realizado para 97 aneurismas (70,8 por cento), clínico para 77 pacientes (70,8 por cento) e contato telefônico para 97 pacientes (91,5 por cento). CONCLUSÃO: Os resultados encontrados nesta série, em termos técnicos, clínicos e angiográficos, são semelhantes aos encontrados na literatura.