marcos rosa júnior - Faculdade de Ciências Médicas da Santa Casa

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MARCOS ROSA JÚNIOR

SPOT SIGN COMO FATOR PREDITOR DE CRESCIMENTO E IMPLICAÇÕES PROGNÓSTICAS NAS HEMORRAGIAS INTRAPARENQUIMATOSAS CEREBRAIS NÃO RELACIONADAS À HIPERTENSÃO ARTERIAL SISTÊMICA

Tese apresentada ao Curso de Pós-Graduação da Faculdade de Ciências Médicas da Santa Casa de São Paulo para obtenção do Título de Doutor em Ciências da Saúde.

SÃO PAULO 2015 (Versão Corrigida)

MARCOS ROSA JÚNIOR

SPOT SIGN COMO FATOR PREDITOR DE CRESCIMENTO E IMPLICAÇÕES PROGNÓSTICAS NAS HEMORRAGIAS INTRAPARENQUIMATOSAS CEREBRAIS NÃO RELACIONADAS À HIPERTENSÃO ARTERIAL SISTÊMICA

Tese apresentada ao Curso de Pós-Graduação da Faculdade de Ciências Médicas da Santa Casa de São Paulo para obtenção do Título de Doutor em Ciências da Saúde. Área de Concentração: Ciências da Saúde. Orientador: Prof. Dr. Antônio José da Rocha

SÃO PAULO 2015

FICHA CATALOGRÁFICA Preparada pela Biblioteca Central da Faculdade de Ciências Médicas da Santa Casa de São Paulo Rosa Júnior, Marcos Spot sign como fator preditor de crescimento e implicações prognósticas nas hemorragias intraparenquimatosas cerebrais não relacionadas à hipertensão arterial sistêmica./ Marcos Rosa Júnior. São Paulo, 2015. Tese de Doutorado. Faculdade de Ciências Médicas da Santa Casa de São Paulo – Curso de Pós-Graduação em Ciências da Saúde. Área de Concentração: Ciências da Saúde Orientador: Antônio José da Rocha 1. Acidente vascular cerebral/diagnósticos 2. Hemorragia cerebral 3. Traumatismos encefálicos 4. Traumatismos craniocerebrais 5. Prognóstico 6. Tomografia computadorizada por raios X BC-FCMSCSP

DEDICATÓRIA

A Deus, Soberano, Forte, Rocha Inabalável, por todos os presentes que me concedeu. À minha esposa, Maressa, O melhor presente que já recebi. Aos meus pais, Marcos e Izabel, que me ensinaram a lutar por meus ideais. Sou eternamente grato por tudo que fizeram por mim. Aos meus irmãos, Gustavo e Ana Carolina, pelo companheirismo e amizade durante nossa caminhada.

Dedicatória

AGRADECIMENTO ESPECIAL

Ao Prof. Dr. Antônio José da Rocha, exemplo de profissional e dedicação. Agradeço por ter me ensinado Neurorradiologia e pelo apoio durante a realização de mais este trabalho. Professor na essência da palavra.

Agradecimento Especial

AGRADECIMENTOS

À Faculdade de Ciências Médicas da Santa Casa de Misericórdia de São Paulo – FCMSCSP – e à Irmandade da Santa Casa de Misericórdia de São Paulo, onde aprendi e me formei radiologista. Ao Serviço de Diagnóstico por Imagem da Santa Casa de São Paulo, por me oferecer excelente formação profissional e um ótimo ambiente de trabalho. À Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) pelo apoio e incentivo durante a realização do projeto. Aos Doutores Antônio Carlos Martins Maia Júnior, Carlos Jorge da Silva e Carlos Toyama por me ensinarem com entusiasmo e dedicação a Neurorradiologia. Aos meus amigos e colegas de trabalho, Bernardo Barros, Douglas Nunes, Felipe Pacheco, Henrique Zuppani, Ingrid Littig, Marcelo Queiroz, Octavio Galvão e Renato Nunes, pela ajuda e amizade. Aos colegas médicos, biomédicos, técnicos, residentes e funcionários do Serviço de Diagnóstico por Imagem da Irmandade da Santa Casa de Misericórdia de São Paulo. Aos meus colegas e alunos da Universidade Federal do Espírito Santo, que também foram importantes na realização deste projeto. Aos pacientes que são a razão maior deste estudo.

Agradecimentos

As benignidades do Senhor mencionarei e os muitos louvores do Senhor, consoante tudo que o Senhor nos concedeu. Isaías 63:7

Citação

ABREVIATURAS

AVC - Acidente Vascular Cerebral Ângio-TC - Angiografia por Tomografia Computadorizada EACA - Ácido ε-Aminocaproico FOV - Campo de Visão HAS - Hipertensão Arterial Sistêmica HIPC - Hemorragia Intraparenquimatosa Cerebral KV - Kilovolts mAs - Miliamperes MIP - Projeção de Intensidade Máxima RM - Ressonância Magnética TC - Tomografia Computadorizada TCE – Traumatismo Cranioencefálico TCLE – Termo de Consentimento Livre e Esclarecido TCMD - Tomografia Computadorizada Multidetectores 3D - Tridimensionais

Abreviaturas

SUMÁRIO

1. INTRODUÇÃO ................................................................................................

1

2. OBJETIVOS.....................................................................................................

6

3. MÉTODOS.......................................................................................................

8

3.1. Pacientes ..................................................................................................

9

3.2. Critérios de inclusão .................................................................................

9

3.3. Critérios de exclusão ................................................................................

10

3.4. Análise das imagens ................................................................................

10

3.5. Análise estatística ....................................................................................

13

4. RESULTADOS ................................................................................................

14

4.1. Artigo 1 .....................................................................................................

15

4.2. Artigo 2 .....................................................................................................

53

5. CONSIDERAÇÕES FINAIS ............................................................................

79

6. REFERÊNCIAS BIBLIOGRÁFICAS................................................................

82

7. ANEXOS .......................................................................................................

91

Sumário

1. INTRODUÇÃO

2

A Hemorragia Intraparenquimatosa Cerebral (HIPC) apresenta várias causas, que podem ser dividas em traumáticas e não traumáticas (espontâneas). A HIPC não traumática representa cerca de 15% dos acidentes vasculares cerebrais (AVC) (Fischbein, Wijman, 2010) e é subdividida em hemorragia primária, causada pela ruptura espontânea de pequenos vasos lesados no contexto da hipertensão arterial sistêmica (HAS) ou pelo depósito de material amiloide em sua parede, no contexto de angiopatia amiloide. É subdividida também em hemorragia secundária, geralmente ocasionadas por lesões vasculares, como aneurismas ou malformações arteriovenosas, além das neoplasias, uso de drogas ou dos distúrbios da coagulação (Siddiqui et al, 2011). O trauma, por sua vez, é a terceira causa de morte no mundo ocidental, sendo o traumatismo cranioencefálico (TCE) responsável por cerca de metade destas mortes. Neste cenário uma lesão comumente encontrada é a contusão cerebral traumática hemorrágica, que traz consigo prognóstico ruim, semelhante as HIPC não traumáticas (Langlois et al, 2006; Alahmadi et al, 2010). Os pacientes com HIPC geralmente se apresentam nas salas de emergência com déficit neurológico focal agudo, crise epiléptica ou alteração do nível de consciência. Esta condição apresenta alta letalidade e risco de incapacidade neurológica permanente, além de prognóstico bastante reservado, estimando-se que mais da metade deles permaneça com sequelas neurológicas após a alta hospitalar (Langlois et al, 2006; Delgado Almandoz, Romero, 2011). Vários fatores relacionados a um prognóstico mais reservado vem sendo estudados na literatura, tanto para as HIPC traumáticas quanto para as HIPC não traumáticas, (Stein et al, 1993; Oertel et al, 2002; Chang et al, 2006; Yadav et al, 2006; Flint et al, 2008; Narayan et al, 2008; Alahmadi et al, 2010; Delgado Introdução

3

Almandoz, Romero, 2011), em particular aqueles fatores que possam ser responsáveis pelo aumento de volume da hemorragia nestes dois grupos de pacientes (Delgado Almandoz, Romero, 2011; Huang et al, 2011; Letourneau-Guillon et al, 2013). Admite-se, entretanto, que o principal fator relacionado ao prognóstico desfavorável seja o volume inicial da HIPC (Wada et al, 2007). O extravasamento do meio de contraste iodado no interior da HIPC foi originalmente descrito na década de 1970 em casos de HIPC primária. Kowada et al (1972), assim como Mizukami et al (1972), relataram poucos casos de extravasamento de contraste no interior da HIPC primária, em estudos de angiografia por cateter. Kowada et al (1972) descreveram 12 pacientes com HIPC primária e observaram extravasamento do meio de contraste iodado em cinco deles, já na fase arterial do estudo angiográfico por cateter. Os focos de extravasamento aumentavam suas dimensões e sua atenuação na fase venosa precoce e esse padrão persistia nas imagens de aquisição tardia. No entanto, foi no final da década de 1990 que surgiram os primeiros estudos na literatura analisando a expansão da HIPC primária por meio da Tomografia Computadorizada (TC). Murai et al (1999) estudaram 31 pacientes com AVC hemorrágico, utilizando angiografia por tomografia computadorizada (ângio-TC) e demonstraram a presença de extravasamento de contraste no interior da HIPC em 5 pacientes, sendo que em três deles documentou-se a expansão da hemorragia nos estudos subsequentes. Becker et al (1999) estudaram a relação do extravasamento do contraste no interior da HIPC primária com a letalidade, demonstrando 63% de letalidade no grupo com extravasamento do meio de contraste iodado no interior da hemorragia e apenas 16% no grupo de pacientes com a ausência de extravasamento. De modo semelhante, Goldstein et al (2007) encontraram maior Introdução

4

letalidade e expansão da hemorragia em pacientes com extravasamento do meio de contraste no interior da HIPC primária, com odds ratio 18 vezes maior de expansão nos casos em que este achado esteve presente. Wada et al (2007) introduziram o termo spot sign pela primeira vez, ao se referirem ao extravasamento do contraste nos casos de HIPC primária e da mesma forma encontraram associação entre a ocorrência deste sinal, visto à TC, e a expansão do hematoma. Na última década foram publicados diversos estudos na literatura internacional, com casuística variável, estudando as características do spot sign e suas relações com expansão da HIPC, letalidade e prognóstico nas HIPC primárias usando a ângio-TC (Goldstein et al, 2007; Wada et al, 2007; Delgado Almandoz et al, 2009; Demchuk et al, 2012). Outro método também utilizado, com este mesmo intuito, foi a ressonância magnética (RM) e Murai et al (1998) descreveram o extravasamento do gadolínio no interior da HIPC, em uma série de 39 pacientes com HIPC primária. Apesar disso, a angiografia por cateter e a RM apresentam algumas limitações para seu uso na rotina das salas de emergência, como a baixa disponibilidade, execução mais difícil, custo relativo alto e a obrigatoriedade de profissional especializado (operador dependente) no caso da angiografia por cateter, deixando a TC como método de escolha para esta análise. Nos casos de TCE postula-se que coagulopatia, necessidade de reanimação cardiopulmonar, idade avançada, desvio das estruturas centromedianas e procedimentos cirúrgicos intracranianos possam ser preditores de aumento do volume das contusões cerebrais traumáticas hemorrágicas (Stein et al, 1993; Oertel et al, 2002; Chang et al, 2006; Yadav et al, 2006; Flint et al, 2008; Narayan et al, 2008; Alahmadi et al, 2010). Entretanto, até o momento, nenhum fator isolado se Introdução

5

confirmou preditor de expansão do componente hemorrágico das contusões cerebrais traumáticas (Oertel et al, 2002; Chang et al, 2006; Narayan et al, 2008). Estudos recentes utilizando tomografia computadorizada multidetectores (TCMD) têm demonstrado que a presença de extravasamento do meio de contraste iodado no interior da HIPC primária (spot sign) constitui forte preditor de crescimento da HIPC primária, levando a um prognóstico ainda mais reservado (Delgado Almandoz, Romero, 2011). Ainda são escassos na literatura, entretanto, estudos científicos sobre a relevância do spot sign nas HIPC secundárias e no cenário do trauma. (Huang et al, 2011; Delgado Almandoz et al, 2012; Letourneau-Guillon et al, 2013). Nos interessamos por este tema no ano de 2011 e iniciamos os estudos das características do spot sign e suas relações nas HIPC primárias e, posteriormente, nas HIPC secundárias, incluindo o trauma.

Introdução

6

2. OBJETIVOS

7

Avaliar a presença e as características do extravasamento ativo do meio de contraste iodado (spot sign) em uma série de pacientes com HIPC secundária e com contusão cerebral traumática, atendidos no serviço de emergência do Hospital Central da Irmandade da Santa Casa de São Paulo. Analisar as relações entre a presença do spot sign, e a expansão, e a letalidade e o prognóstico das contusões cerebrais traumáticas. Estudar as relações entre a ocorrência do spot sign e a letalidade da HIPC secundária.

Objetivos

8

3. MÉTODOS

9

3.1. Pacientes

Este estudo faz parte de um projeto maior que usa a TCMD para avaliar o AVC hiperagudo/agudo e as contusões cerebrais traumáticas; os protocolos foram separadamente revisados e aprovados pelo Comitê de Ética em Pesquisa da Irmandade da Santa Casa de Misericórdia de São Paulo e todos os pacientes ou seus responsáveis legais assinaram o Termo de Consentimento Livre e Esclarecido (Anexos 1 e 2). Participaram do estudo indivíduos com contusão cerebral traumática atendidos no Hospital Central da Irmandade da Santa Casa de Misericórdia de São Paulo, consecutivamente, no período compreendido entre agosto de 2011 a outubro de 2014. Estudamos também indivíduos com HIPC secundária atendidos no mesmo hospital, consecutivamente, no período compreendido entre agosto de 2011 a maio de 2013. Os pacientes foram monitorados em unidades de terapia intensiva ou em sala de emergência e tratados de acordo com as recomendações para o manejo da HIPC (Pontes-Neto et al, 2009) e da contusão cerebral traumática (Bullock et al, 2006).

3.2. Critérios de inclusão

1. Indivíduos de todas as idades com HIPC de causa secundária confirmada através de TC, ressonância magnética, angiografia digital, biopsia ou cirurgia. 2. Indivíduos de todas as idades que chegaram ao hospital com contusão cerebral traumática hemorrágica evidenciada na TC sem a administração intravenosa do meio de contraste iodado.

Métodos

10

3. Indivíduos que realizaram a TC em até 72 horas após o icto e que o maior eixo do componente hemorrágico foi ≥ 2,0 cm. 4. Concordância em participar do estudo, dada pelo paciente ou seu responsável.

3.3. Critérios de exclusão

1. Impossibilidade de acesso venoso para a administração do contraste iodado por bomba injetora. 2. História de alergia específica ou contraindicação ao uso de contraste iodado. 3. Exames de imagem com técnica inadequada ou com artefatos que prejudiquem a análise. 4. Pacientes com HIPC primária.

3.4. Análise das Imagens

Todos os exames de imagem foram realizados com doses mínimas de radiação e contraste iodado intravenoso em aparelho de TCMD com 64 fileiras de detectores (Brilliance CT 64 Channel, Philips Medical, Eindhoven, The Netherlands), nas fases sem contraste, arterial (precoce) e venosa (tardia) da ângio-TCMD. Sendo o exame de TC realizado com 120 kilovolts (KV) e 185 milliamperes (mAs), com 450 mm de campo de visão (FOV) e pitch de 0.673. A fase arterial (precoce) da ângioTCMD foi realizada 20 segundos após a injeção do contraste iodado em veia periférica, usando bomba injetora de duas cabeças (Medrad, Warrendale, USA), com velocidade de infusão de 4–6 ml/s, com acesso 18-G para adultos e 22-G em crianças, na dose de 1,0 ml/Kg. A fase venosa (tardia) da ângio-TCMD foi realizada Métodos

11

com os mesmos parâmetros, 60 segundos após a injeção do contraste iodado intravenoso. A interpretação das imagens incluiu a análise da TC sem contraste, as imagens fonte da ângio-TCMD nas fases arterial e venosa, bem como as reconstruções com projeção de intensidade máxima (MIP) e tridimensionais (3D). Todas as imagens foram processadas usando estação de trabalho (Extended Brilliance Workspace v3.5.0.2250, Philips Medical Systems Nederland B.V., PC Best, The Netherlands). A análise das imagens foi realizada por dois neurorradiologistas (MRJ e AJR) com experiência na interpretação de estudos de TC e ângio-TCMD, em consenso, visando identificar a presença ou ausência do spot sign, conforme critérios estabelecidos por Delgado Almandoz, Romero (2011), apresentado no Quadro 1. QUADRO 1. Critérios para identificação do spot sign. Identificação do spot sign Qualquer foco de extravasamento do meio de contraste iodado no interior da hemorragia Ausência de continuidade com vasos normais ou anormais adjacentes à hemorragia Atenuação > 120 Unidades Hounsfield

Categorizamos nossa série de pacientes quanto ao escore do spot sign, avaliando o número de focos de extravasamento do meio de contraste iodado no interior da hemorragia, bem como a maior dimensão deste foco e a atenuação em unidades Hounsfield, para construir o escore do spot sign, como previamente proposto (Delgado Almandoz et al, 2010), e demonstrado no Quadro 2.

Métodos

12

QUADRO 2. Escore do spot sign.

Para a análise comparativa, nos indivíduos com contusão cerebral traumática, o volume da HIPC foi calculado conforme proposto na literatura por Divani et al (2011), utilizando a primeira TC sem contraste e a TC de controle, multiplicando-se os três maiores eixos da HIPC e o resultado desta multiplicação por 0,5 (AP x CC x LL x 0,5). A expansão da hemorragia foi determinada na TC sem contraste iodado intravenoso, realizada no acompanhamento, conforme a indicação e o melhor juízo clínico, sem a interferência deste protocolo de estudo na indicação do exame. A área de edema vasogênico perilesional e a eventual coexistência de hemorragia extraaxial não foram considerados para o cálculo. Nem todos os pacientes com contusão cerebral traumática de nossa casuística realizaram TC controle durante o acompanhamento hospitalar. Estes pacientes, portanto, não foram estudados com relação à expansão do componente hemorrágico. Entretanto, como nós tínhamos o desfecho destes pacientes durante a evolução, decidimos mantê-los no estudo para analisar sua evolução prognóstica e risco de morte. No estudo dos indivíduos com HIPC de causa não traumática enfrentamos as mesmas dificuldades de outros estudos já relatados na literatura internacional, não Métodos

13

sendo possível a avaliação da expansão da hemorragia, visto que a maioria destes pacientes usualmente são submetidos ao tratamento cirúrgico logo após o primeiro estudo tomográfico (Delgado Almandoz et al, 2012; Brouwers et al, 2013). Neste grupo de pacientes portanto, estudamos as relações do spot sign com a letalidade. A

expansão

do

componente

hemorrágico

das

contusões

cerebrais

traumáticas foi avaliada de forma semelhante aos parâmetros já propostos por outros autores, definida quando a hemorragia aumentou em mais de 6 ml ou em mais de 33% de seu volume inicial (Huang et al, 2011; Demchuk et al, 2012; Letourneau-Guillon et al, 2013; Rosa Jr et al, 2013). Os pacientes com contusão cerebral traumática foram categorizados como prognóstico desfavorável quando apresentaram expansão da hemorragia, necessidade de cirurgia para drenagem da contusão hemorrágica ou quanto morreram durante a internação hospitalar.

3.5. Análise estatística

Realizamos análise univariada e multivariada para estudar as variáveis relacionadas. Na análise univariada empregamos o teste exato de Fisher e o teste de igualdade das médias para determinar as relações entre as variáveis com a letalidade, prognóstico e a expansão da HIPC. Utilizamos também uma regressão logística multivariada para identificar variáveis independentes na expansão da hemorragia e na letalidade. Foi considerado estatisticamente significante o valor p < 0,05.

Métodos

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4. RESULTADOS

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Seção: Articles – Article 1

Resultados

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Title: Contusion contrast extravasation depicted on multidetector computed tomography angiography predicts growth and mortality in traumatic brain contusion.

Short title: Contrast extravasation in traumatic brain contusion.

Authors: Marcos Rosa Júnior,1,2 Antônio José da Rocha,1 Antônio Carlos Martins Maia Júnior,1 Nelson Saade,3 José Carlos Esteves Veiga,3 Javier M. Romero.4 1

– Section of Neuroradiology, Santa Casa de Misericórdia de São Paulo, São Paulo

SP, Brazil. 2

– Section of Radiology, Federal University of Espírito Santo, Vitória ES, Brazil.

3

– Division of Neurosurgery, Santa Casa de Misericórdia de São Paulo, São Paulo

SP, Brazil. 4

– Division of Neuroradiology, Massachusetts General Hospital, Harvard Medical

School, Boston, MA, USA. There is no conflict of interest to declare. There is no funding source. Category for the manuscript: original research. Correspondence to: Marcos Rosa Júnior, MD Santa Casa de Misericórdia de São Paulo – Serviço de Diagnóstico por Imagem Rua Dr. Cesário Motta Junior 112, Vila Buarque, São Paulo – SP / Brazil Postal code: 01221-020 Phone: +55 11 21767323 Fax: +55 11 21767321 e-mail: [email protected] Resultados

17

Abstract

Traumatic brain injury (TBI) is the main cause of death in trauma victims and causes high rates of disability and neurological sequelae. Approximately 38-65% of traumatic brain contusions (TBC) demonstrate hemorrhagic expansion on serial computed tomography (CT) scans. However, thus far, no single variable can accurately predict the hemorrhage expansion of a TBC. Purpose: To evaluate contrast extravasation (CE) as a predictor of expansion, mortality and poor outcome in TBC in a Brazilian cohort. Materials and Methods: After institutional review board approval, we used multidetector computed tomography angiography (MDCTA) to study 121 consecutive patients (106 men, 87.6%) with ages varying from 10 to 85 years. Informed consent was obtained from all subjects. The clinical and imaging findings were correlated with the findings on the initial MDCTA using either Fisher’s exact test or Student’s t-test and a multivariate logistic regression model. Results: Of the individuals who presented CE in TBC, 21.8% died (in-hospital mortality), whereas in the absence of this sign, the mortality rate was 7.6% (p = 0.014). Additionally, expansion of the hemorrhagic component of the TBC was detected in 61.1% of the CE-positive patients, whereas expansion was only observed in 10% of the CE-negative patients (p < 0.001). Poor outcome was observed in 24.2% of the patients in the CE-negative group, but in the presence of CE, 72.7% evolved with poor outcome (p < 0.001). Conclusions: The CE was a strong independent predictor of expansion, poor outcome, and increased risk of in-hospital mortality in our series of patients with TBC. Keywords: contrast extravasation, spot sign, multidetector CT angiography, traumatic brain contusion, traumatic brain injury.

Resultados

18

Introduction

Traumatic brain injury (TBI) is the main cause of death in trauma victims.1 Traumatic brain contusion (TBC) is a frequent finding and often causes cognitive, behavioral and emotional impairments.2-4 Approximately half of the survivors of TBI have been reported to develop long-term disabilities,3-5 and approximately 38-65% of the patients with TBC have demonstrated hemorrhagic progression of a contusion on serial computed tomography (CT) scans.6-13 Non-contrast CT (NCCT) has played a key function in patients with TBI, given its high sensitivity for the detection of hemorrhagic lesions.14 Several

factors

such

as

concomitant

coagulopathy,

the

need

for

cardiopulmonary resuscitation, old age, multiple hematomas, midline shift, surgical decompressive procedures, initial TBC size and the presence of subdural hematoma have been associated with radiological expansion of the hemorrhagic component of the TBC.7,10,13,16,17 However, thus far, no single variable accurately predicts this serious progression.8,10,11 Active contrast extravasation (CE) on computed tomography angiography (CTA) has been intensively studied in primary17-24 and secondary intracerebral hemorrhage (ICH).25,26 In non-traumatic ICH, CE on CTA has been confirmed to predict hematoma expansion, poor outcome and high mortality.17-24 Despite some reports on CT identification of CE in head trauma,14,27,28 there are only a few studies on this topic.14,27 Furthermore, it remains necessary to reproduce the CTA results and evaluate the prognostic implications of the CE in this population of patients with TBI in a larger series.

Resultados

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Our main aim is to study the CE characteristics’ on CTA-source images (CTASI) and estimate their relationship with expansion of the hemorrhagic component of the TBC, poor outcome and mortality rate in a Brazilian cohort of patients with TBI. The relevance of this study derives from the potential reproducibility of CTA technique as a daily routine to evaluate this not uncommon scenario, which often demands intensive care and determines serious neurological sequelae in economically active persons around the world.

Materials and Methods

Patients

After institutional review board approval, we prospectively analyzed patients of any age or gender who presented to the emergency department with a clinical history of TBI wherein the hemorrhagic component of TBC measured > 2.0 cm on any axis, demonstrated on NCCT, from August 2011 to October 2014. Informed consent was obtained from all subjects (signed personally or by their guardians). CTA with comparable imaging parameters was performed on patients who arrived at the hospital within the first three days after brain trauma. We excluded patients with contraindications to the administration of the intravenous iodine contrast agent, patients who refused to participate in the study, and patients whose examination quality was considered inadequate or contained technical artifacts. Clinical history and laboratory results were reviewed to identify arterial hypertension diagnosis or diabetes mellitus and to confirm coagulation disorders. A Resultados

20

coagulation disorder was defined as any disturbance in a patient’s coagulation parameters, including prolongation of the pro-thrombin time (PT), [PT < 70%], elevation of the International Normalized Ratio (INR), [INR ≥ 1,4], elevation of the activated partial thromboplastin time (aPTT), [aPTT > 38 seconds] or a decrease in the platelet number (PLT), [PLT < 100,000]. All patients were monitored in the intensive care unit or emergency room and treated according to the current guidelines for the management of brain contusion.29 All imaging exams were conducted using a 64-slice CT scanner (Brilliance CT 64 Channel, Philips Medical, Eindhoven, North Brabant, The Netherlands), adding CTA to the first requested NCCT. The CTA examination was performed using 120 kilovolts (KV) and 185 milliamperes (mAs), a 450 mm field of view (FOV), 0.6 mm section thickness and a pitch of 0.673. The first acquisition (arterial phase) was performed after a time delay of 20 seconds by injecting iodine contrast at 4–6 mL/s in a dual-head power injector (Medrad, Warrendale, PA, USA) with an appropriate intravenous access, which was generally 18-G in adults and 22-G in children, located in a peripheral vein, at a dose of 1.0 mL/kg. The additional acquisition of CTA (venous phase) was obtained using identical parameters 60 seconds after the beginning of the contrast administration. The control imaging study was performed according to clinical judgment, using only a standardized NCCT, within the first three days after admission, without interference from this study.

Imaging analysis

The imaging interpretation included analysis of the NCCT and CTA-SI, as well as the maximum intensity projection (MIP) and tridimensional (3D) post-processed Resultados

21

views of CTA. All data were post-processed using commercially available software on a workstation (Extended Brilliance Workspace v3.5.0.2250, Philips Medical Systems Nederland B.V., PC Best, The Netherlands). All images were evaluated by 2 neuroradiologists with 19 and 4 years of experience in the diagnosis of TBC and in the interpretation of CTA. Differences in reader interpretation regarding the presence or characteristics of CE were decided by consensus. The CE was considered to be present or absent on CTA-SI adapted according to previously reported criteria proposed for primary ICH:19 one or more focus of contrast pooling within a TBC (of any size and morphology), discontinuity from normal or abnormal vasculature adjacent to the TBC, and attenuation > 120 Hounsfield Units (UH). To comparatively categorize our cohort of subjects, we considered the number of foci of CE within the TBC, the largest dimension of focus and attenuation in HU to build a contrast extravasation score (CES), as previously proposed for primary ICH.19,30 The volume of the hemorrhagic component of the TBC was calculated on the first NCCT scan, estimating its three major axes and multiplying the result by 0.5. The perilesional areas of vasogenic edema and extra-axial hemorrhage were not considered in the volume measurement. NCCT data were also assessed for subarachnoid hemorrhage, subdural hematoma, intraventricular hemorrhage and midline shift. Midline shift was measured at the level of the foramen of Monro. Expansion of the hemorrhagic component of the TBC was defined at the follow-up NCCT by an absolute growth greater than 6 mL or a relative growth of more than 33% from the initial NCCT, in accordance with other ICH studies.18,24 A poor outcome was defined when an expansion of the hemorrhagic component of the TBC Resultados

22

occurred at the follow-up NCCT, when the patient died or when surgery was necessary to treat the TBC.

Statistical analysis

Univariate analysis using either Fisher’s exact test or Student’s t-test was performed to determine the relationship between the presence of CE within the TBC and expansion, poor outcome and in-hospital mortality. We also used a multivariate logistic regression model to identify the independent predictors of TBC expansion, the presence of CE and in-hospital mortality. The results were considered to be statistically significant when p < 0.05. The data were analyzed by using the Statistical Package for Social Sciences (SPSS) statistical software, version 14.0 (SPSS Inc., Chicago, IL, USA).

Results

According to the inclusion criteria, 188 subjects were consecutively selected during the defined period. A total of 67 patients (67/188 – 35.6%) were subsequently excluded: 16 subjects (16/188 – 8.5%) diagnosed with TBC less than 2.0 cm along the longest axis, 6 additional subjects (6/188 – 3.2%) diagnosed with TBC but not within the first 3 days of the trauma, 34 (34/188 – 18.1%) excluded due to unavailable peripheral venous access to obtain CTA images, and 11 (11/188 – 5.8%) excluded due to artifacts in the images.

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We finally enrolled 121 subjects (121/188 – 64.4%) diagnosed with TBC into the current study. Demographic data, the initial volume of the hemorrhagic component of the TBC and the elapsed time between the trauma and the first CTA were all analyzed (Appendix.1 and Table.1). The CE on CTA-SI was documented in 55 subjects (55/121 – 45.4%), (Fig. 1). All cases of CE (55/55 – 100%) were detected during the venous phase of CTA-SI in our series. Conversely, this imaging sign was only detected in 44 subjects during the arterial phase of CTA-SI (44/55 – 80.0%). The initial average volume of the hemorrhagic component of the TBC was 16.4 mL (range, 1 – 187 mL). The average volume was 24.7 ml in the CE-positive group (range, 1.6 – 187 mL) and 9.5 mL in the CE-negative group (range, 1 – 105 mL) (p = 0,008). The CE was documented up to 72 hours after trauma, with a mean of 11 hours (range, 1 – 72 hours) and a median of 6 hour (interquartile range [IQR], 4 – 14 hours). When categorizing patients according to the CES, we found 25 patients with CES 1 (25/55 – 45.4%), 22 with CES 2 (22/55 – 40.0%), 5 with CES 3 (5/55 – 9.1%) and 3 additional patients with CES 4 (3/55 – 5.5%) (Table 2). Hemorrhagic expansion of a TBC was documented in 10.0% (6/60) of patients in the CE-negative group and in 61.1% (22/36) (p < 0.001) of the CE-positive group (Fig. 2). A poor outcome was registered in 24.2% (16/66) of the patients in the CEnegative group and in 72.7% (40/55) of the patients in the CE-positive group (p < 0.001). A mortality rate of 7.6% (5/66) was documented in CE-negative group, whereas the CE-positive group exhibited 21.8% (12/55) in-hospital mortality (p = 0.014).

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Table 3 provides a summary of clinical and CTA predictors of CE and mortality in our series of patients. Table 4 provides a summary of the clinical and CTA predictors of TBC expansion. Multivariate logistic regression was used to analyze certain additional features, including age, gender, TBC location and volume, CE, midline shift, subarachnoid hemorrhage, subdural hematoma, ventricular hemorrhage and Glasgow Coma Scale Score (GCS). Mortality was primarily influenced by GCS and CE, whereas expansion of the hemorrhagic component of the TBC was influenced by CE in multivariate logistic regression.

Discussion

Recent studies have showed that 38 to 65% of TBCs present expansion of the hemorrhagic component.6-13 In our series, the expansion of the hemorrhagic component of the TBC was observed in 29.1% of our patients, somewhat lower than previously reported in the literature, probably due to our restricted selection criteria, which selected patients within up to 72 hours after injury. This criterion probably included a comparative bias to select patients who suffered less severe traumatic brain injury. Most reports limit the selection to 6 h or 24 h after injury.14,27 The inconsistent definition for hematoma expansion has been debated in current literature.18,19 Several expansion thresholds have previously been proposed, including any increase in the hemorrhage or 20%, 25%, 30% or 33% growth to define expansion of the hemorrhage; other studies have used an increase of 5 mL, 6 mL, or 12 mL to define expansion. To ensure the clinical significance of our results, we decided to use a stricter threshold in accordance with other ICH studies.18,24 Resultados

25

The expansion of the hemorrhagic component of the TBC is relevant because it worsens the prognosis of patients, as it might promote increased mass effect and higher intracranial pressure.6 No single variable can yet accurately predict the expansion of the hemorrhagic component of the TBC; however, several features have been studied as possible predictors of expansion, including coagulopathy, the need for cardiopulmonary resuscitation, old age, multiple hematomas, midline shift, surgical decompressive procedures, initial size of the TBC and presence of subdural hematoma.6-16 Alahmadi et al.7 found that the presence of subdural hematoma and initial hemorrhage volume are predictors of expansion of the TBC. Our data enlarge this knowledge to include coagulopathy, subarachnoid hemorrhage and mainly CE as predictors of expansion of the TBC. The CE was an independent predictor of expansion of the hemorrhagic component of the TBC in multivariate logistic regression. Similar to prior TBC studies,14,27 our results demonstrate the prognostic value of CE in TBI. However, compared with previous reports,

14,27

the current one

included a larger population. MR imaging series have evaluated the focal enhancement of traumatic hematomas31,32 and CE in non-traumatic ICH,33 similarly suggesting a predictive value of CE in these settings. The occurrence of CE in our series was 45.4%, agreeing with previous studies, which have reported values varying from 40.9 to 50%.14,27 It is known that early arrival to the hospital is related to a higher frequency of CE within the TBC.27 Our results are consistent with this tendency, although the findings most strongly associated with the occurrence of the CE were the presence of subdural hematoma and ventricular hemorrhage rather than time of arrival at hospital. Because subdural hematoma and ventricular hemorrhage are predominantly determined by venous bleeding, early imaging acquisition and the presence of subdural hematoma and Resultados

26

ventricular hemorrhage are likely intrinsically correlated. The presence of CE was more frequent in our series in patients who came to the hospital sooner but also occurred in patients who arrived later, likely as a marker of more severe parenchymal laceration in the latter case. Our study also showed that the initial average volume of the hemorrhagic component of the TBC was higher in the CE-positive group, suggesting that it may represent a marker of more severe parenchymal laceration in these individuals. The venous phase of CTA has been reported to increase the detection of CE by 8-23% in primary ICH.19 Similarly, the venous phase of CTA was also the most important for the detection of CE in our series of patients with TBC, allowing for additional detection in 20% of the patients compared with the arterial phase of CTA. None of our patients were suspected of traumatic vessel injury, and the arterial phase of CTA did not show any unsuspected lesions in either the large or middle arteries. Thus, we argue that in this setting, the venous phase of CTA (60 seconds delayed) is sufficient to detect CE and to estimate the expansion of the hemorrhagic component of the TBC. It is important to reduce radiation exposure, primarily in young patients, when arterial traumatic lesions are not suspected. However, more studies are needed to determine the real importance of the arterial phase of CTA in this setting. To the best of our knowledge, this work is the first MDCT study of TBC to apply the CE score proposed by Delgado-Almandoz et al. in primary ICH30 to TBI. We found that the higher score (CES) is significantly correlated with the expansion of the hemorrhagic component of the TBC, with a higher mortality rate and with a worse prognosis of these patients. However, verification of the reproducibility of this score remains necessary in this particular setting. Resultados

27

Coagulopathy is reported to occur in patients with TBI upon admission with some variability,34 but Harhangi et al.35 reported an overall prevalence of 32.7%. Coagulopathy was observed in 28.9% of our patients, similar to the findings of Harhangi. Although Smith et al.36 found no association between the presence of coagulopathy and the expansion of the TBC in their studies, we found a statistically significant association between coagulopathy and expansion in 48% of patients, whereas Allard et al.37 found expansion in 80% of patients with coagulopathy compared with the 36% observed for patients without coagulopathy. A recent review of hemostatic drugs for TBI has concluded that there is no reliable evidence from randomized controlled trials to support the effectiveness of hemostatic drugs in reducing mortality or disability in patients with TBI.38 However, this issue is important, and additional trials are still required.39 In agreement with a previous report,14 we found an association of the CE with in-hospital mortality and poor outcome. Though a poor outcome was observed in 24.2% of patients in CE-negative patients, in the presence of CE, 72.7% of our patients exhibited poor outcomes. The mortality rate was also significantly higher when CE was found on CTA-SI. Our report has certain limitations, including the delayed arrival of the patients to our center, which may have biased the study toward the inclusion of less severe TBIs. Long-term prognosis was not considered because the focus of this study was primarily the acute in-hospital course. Another limitation is the volume calculation method. Although computer-aided planimetry shows fewer errors and improved performance for irregularly shaped hematomas,40 we used the ABC/2 method because it is more routine, easier and widely used in the literature.41

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28

The authors encourage the use of CTA, particularly the venous phase, in an imaging work-up for TBI, in patients with TBC, even to study patients who arrived at the hospital after the first six hours of trauma. CTA-SI was shown to be useful for detecting CE, even up to 72 hours after trauma, which was positively associated with expansion of the hemorrhagic component of the TBC, poor outcome and in-hospital mortality. Further studies on this topic remain needed to improve care for this serious neurological effect, particularly with the use of hemostatic procedures.

Author Disclosure Statement No competing financial interests exist.

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29

Table 1 – The demographic and clinical data of our series of patients, with the presence of contrast extravasation.

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

1

M

32

6

70.0

Y

1

+

+

2

M

70

5

11.7

Y

1

+

+

3

F

45

12

4.1

Y

2

+

+

4

M

30

24

6.5

Y

1

-

+

5

M

52

3

4.6

Y

3

+

+

6

M

46

9

114.9

Y

2

+

+

7

M

67

4

6.0

Y

2

+

+

8

M

39

24

47.2

Y

2

-

+

9

M

52

4

21.4

Y

2

+

+

10

M

48

3

7.2

Y

3

+

+

11

M

56

6

15.1

Y

1

+

+

12

M

67

3

1.8

Y

1

+

+

13

M

56

4

5.0

Y

1

+

+

14

M

29

4

10.0

Y

2

+

+

15

M

43

4

13.5

Y

1

+

+

16

M

51

24

13.6

Y

2

+

+

17

F

10

4

4.3

Y

3

+

+

18

M

19

3

4.0

Y

1

+

+

19

M

50

3

61.5

Y

2

+

+

20

M

40

5

140.4

Y

2

-

+ Resultados

30

continuation Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

21

F

78

7

7.5

Y

4

+

+

22

M

50

4

40.0

Y

2

+

+

23

F

56

3

2.5

Y

2

+

+

24

M

54

7

1.7

Y

2

+

+

25

F

15

9

2.1

Y

1

-

+

26

M

58

6

4.3

Y

2

+

+

27

M

61

6

27.7

Y

2

+

+

28

M

17

4

40.9

Y

2

+

+

29

M

22

7

10.6

Y

2

+

+

30

M

16

3

13.1

Y

1

+

+

31

M

45

9

52.3

Y

2

+

+

32

M

38

24

13.9

Y

1

+

+

33

M

55

9

32.1

Y

1

-

+

34

F

70

13

2.3

Y

1

-

+

35

M

81

72

13.6

Y

2

+

+

36

M

64

9

28.5

Y

1

+

+

37

M

35

14

9.8

Y

1

+

+

38

M

42

24

40.8

Y

1

+

+

39

M

18

3

187.0

Y

4

+

+

40

M

65

12

7.0

Y

3

-

+

41

M

45

48

4.2

Y

1

-

+

42

M

58

2

2.0

Y

1

-

+

43

M

50

4

47.4

Y

1

+

+

Resultados

31

continuation Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

44

F

65

6

1.7

Y

2

+

+

45

M

30

4

26.1

Y

4

+

+

46

M

81

3

1.7

Y

1

-

+

47

M

50

18

55.5

Y

2

+

+

48

M

37

18

6.3

Y

1

+

+

49

M

59

12

3.8

Y

1

+

+

50

M

34

24

15.5

Y

2

+

+

51

M

55

1

13.1

Y

3

+

+

52

M

65

24

2.2

Y

2

+

+

53

M

45

24

75.6

Y

1

+

+

54

M

71

17

1.7

Y

1

+

+

55

M

33

4

1.6

Y

1

-

+

F – female / M – male. N – No / Y – Yes. TIME – time between the trauma and the first CTA. VOLUME – volume of the hemorrhagic component of the TBC. * – CE: Contrast extravasation. ** – CES: Contrast extravasation score. *** – Contrast extravasation detected on arterial (CE artery) or venous (CE venous) phases of computed tomography angiography (CTA).

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Table 2 – Contrast extravasation score (CES) and its relationships with expansion, mortality and poor outcome.* Poor   CES  

N  

N2   Expansion   Mortality  

Expansion  %  

Mortality  %  

Poor  outcome  %      

outcome       0  

66  

60  

6  

5  

16  

10.0  

7.6  

24.2  

1  

25  

18  

10  

4  

16  

55.6  

16.0  

64.0  

2  

22  

14  

8  

4  

16  

57.1  

18.2  

72.7  

3  

5  

3  

3  

2  

5  

100.0  

40.0  

100.0  

4  

3  

1  

1  

2  

3  

100.0  

66.7  

100.0  

0.8  (0.7-­‐0.9)  

0.68  (0.54-­‐0.83)  

0.76  (0.67-­‐0.85)  

 

 

 

  <0.001  

0.014  

<0.001  

 

 

 

 

AUC   (95%  CI)   P  value  

 

CES – Contrast extravasation score.

 

N – Total number of patients. N2 – Total number of patients with CT control. AUC – Area under curve CI – Confidence interval * – Adapted from spot sign score.30

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Table 3 – Clinical and CTA predictors of the contrast extravasation (CE) and mortality in our series of patients. CE, n (%)

p Value*

In-hospital mortality, n (%) p Value*

55 (45.4)

NA

17 (14.0)

NA

Male, n=106

48 (45.3)

1

15 (14.1)

1

Female, n=15

7 (46.7)

2 (13.3)

≤45, n=57

24 (42.1)

8 (14.0)

46-70, n=53

27 (50.9)

>71, n=11

4 (36.4)

3 (27.3)

≤3, n=19

11 (57.9)

3 (15.8)

>3 - ≤6, n=40

18 (45.0)

>6, n=62

26 (41.9)

All patients, n=121 Sex

Age, years

0.60

6 (11.3)

0.34

Time from trauma, h

0.46

7 (17.5)

0.78

7 (11.3)

Blood glucose ≥ 170 mg/dl No, n=109

48 (44.0)

Yes, n=12

7 (58.3)

0.71

14 (12.8)

0.02

3 (25.0)

Resultados

34

Continuation

CE, n (%)

p Value*

In-hospital mortality, n (%) p Value*

CD Unknown, n=37

13 (35.1)

2 (5.4)

No, n=49

22 (44.9)

Yes, n=35

20 (57.1)

10 (28.6)

≤20, n=96

37 (38.5)

9 (9.4)

>20 - ≤50, n=15

10 (66.7)

>50, n=10

8 (80.0)

4 (40.0)

≤8, n=18

9 (50.0)

9 (50.0)

9-12, n=22

11 (50.0)

>13, n=81

35 (43.2)

0.37

5 (10.2)

0.04

ICH volume, mL

0.008

4 (26.7)

0.01

Admission GCS

0.31

3 (13.6)

<0.001 x

5 (6.1)

Blood hypertension >140x90 mmHg

No, n=75

33 (44.0)

Yes, n=46

22 (47.8)

0.71

9 (12.0)

0.42

8 (17.4)

Midline shift No, n=90

40 (44.4)

Yes, n=31

15 (48.4)

0.44

11 (12.2)

0.37

6 (19.3)

Resultados

35

Continuation

CE, n (%)

p Value*

In-hospital mortality, n (%) p Value*

No, n=38

10 (26.3)

0.006

2 (5.3)

Yes, n=83

45 (54.2)

Subarachnoid hemorrhage 0.08

15 (18.1)

Subdural hematoma No, n=45

12 (26.7)

Yes, n=76

43 (56.6)

0.002

2 (4.4)

0.02

15 (19.7)

Ventricular hemorrhage No, n=96

37 (38.5)

Yes, n=25

18 (72.0)

0.003 x

10 (10.4)

0.04

7 (28.0)

*Univariate analysis. x – Multivariate logistic regression analysis. GCS – Glasgow Coma Scale. CD – Coagulation disorder. CE – Contrast extravasation.

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36

Table 4 – Clinical and CTA predictors of expansion of the hemorrhagic component of the traumatic brain contusion in our series of patients. Expansion, n (%)

p Value**

28 (29.2)

NA

Male, n=83

25 (30.1)

0.75

Female, n=13

3 (23.1)

All patients*, n=96 Sex

Age, years ≤45, n=40

8 (20.0)

46-70, n=46

17 (36.9)

71-95, n=10

3 (30.0)

0.21

Time from trauma, h ≤3, n=14

6 (42.8)

>3 - ≤6, n=29

10 (34.5)

>6, n=53

12 (22.6)

0.24

Blood glucose ≥ 170 mg/dl No, n=87

25 (28.7)

Yes, n=9

3 (33.3)

0.59

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37

Continuation

Expansion, n (%)

p Value**

CD Unknown, n=30

6 (20.0)

No, n=41

10 (24.4)

Yes, n=25

12 (48.0)

0.03

ICH volume, mL ≤20, n=84

25 (29.8)

>20 - ≤50, n=10

2 (20.0)

>50, n=2

1 (50.0)

0.62

Admission GCS ≤8, n=14

7 (50.0)

9-12, n=13

4 (30.8)

>13, n=69

17 (24.6)

0.25

Blood hypertension >140x90 mmHg

No, n=59

15 (25.4)

Yes, n=37

13 (35.1)

0.36

Midline shift No, n=77

22 (28.6)

Yes, n=19

6 (31.6)

0.78

Resultados

38

Continuation

Expansion, n (%)

p Value**

No, n=33

5 (15.1)

0.03

Yes, n=63

23 (36.5)

Subarachnoid hemorrhage

Subdural hematoma No, n=40

6 (15.0)

Yes, n=56

22 (39.3)

0.01

Ventricular hemorrhage No, n=80

20 (25.0)

Yes, n=16

8 (50.0)

0.06

Contrast extravasation No, n=60

6 (10.0)

Yes, n=36

22 (61.1)

<0.001 x

* Only patients with control CT. ** Univariate analysis. x – Multivariate logistic regression analysis. GCS – Glasgow Coma Scale. CD – Coagulation disorder.

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Appendix 1 –The demographic and clinical data of our series of patients. Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

1

M

32

24

12.0

N

0

2

M

32

6

70.0

Y

1

+

+

3

M

60

3

12.8

N

0

4

M

56

4

2.8

N

0

5

M

70

5

11.7

Y

1

+

+

6

F

45

12

4.1

Y

2

+

+

7

M

46

4

20.2

N

0

8

M

26

6

25.4

N

0

9

M

30

24

6.5

Y

1

-

+

10

M

72

16

2.7

N

0

11

M

52

3

4.6

Y

3

+

+

12

M

46

9

114.9

Y

2

+

+

13

M

67

4

6.0

Y

2

+

+

14

M

42

12

1.0

N

0

15

M

39

24

47.2

Y

2

-

+

16

M

41

24

19.7

N

0

17

M

68

6

6.1

N

0

18

M

51

24

5.3

N

0

19

M

29

13

1.0

N

0

20

M

52

4

21.4

Y

2

+

+

21

M

40

24

12.8

N

0

22

F

29

24

8.6

N

0

23

M

48

3

7.2

Y

3

+

+

Resultados

40

Continuation

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

24

M

44

12

2.3

N

0

25

M

21

12

2.0

N

0

26

M

53

3

4.8

N

0

27

M

63

2

1.5

N

0

28

M

62

4

5.8

N

0

29

M

56

6

15.1

Y

1

+

+

30

M

67

3

1.8

Y

1

+

+

31

M

24

18

5.9

N

0

32

M

43

15

8.4

N

0

33

M

56

4

5.0

Y

1

+

+

34

M

47

3

1.7

N

0

35

M

85

3

6.1

N

0

36

M

24

5

12.0

N

0

37

M

29

4

10.0

Y

2

+

+

38

M

68

3

59.1

N

0

39

M

53

5

1.0

N

0

40

M

28

4

1.2

N

0

41

M

39

6

6.5

N

0

42

M

61

4

6.0

N

0

43

M

43

4

13.5

Y

1

+

+

44

M

45

7

22.5

N

0

45

M

51

24

13.6

Y

2

+

+

46

M

27

7

1.0

N

0

Resultados

41

Continuation

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

47

F

10

4

4.3

Y

3

+

+

48

M

17

5

1.6

N

0

49

M

77

18

7.2

N

0

50

M

66

12

19.5

N

0

51

M

57

3

2.6

N

0

52

M

51

5

3.1

N

0

53

M

49

6

7.0

N

0

54

M

19

3

4.0

Y

1

+

+

55

M

50

3

61.5

Y

2

+

+

56

M

52

4

8.2

N

0

57

F

43

6

2.1

N

0

58

M

40

5

140.4

Y

2

-

+

59

F

78

7

7.5

Y

4

+

+

60

M

50

4

40.0

Y

2

+

+

61

M

41

3

3.1

N

0

62

F

56

3

2.5

Y

2

+

+

63

M

54

7

1.7

Y

2

+

+

64

M

18

24

5.5

N

0

65

F

15

9

2.1

Y

1

-

+

66

M

58

6

4.3

Y

2

+

+

67

F

19

10

4.7

N

0

68

M

61

6

27.7

Y

2

+

+

69

M

17

4

40.9

Y

2

+

+

Resultados

42

Continuation

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

70

M

22

7

10.6

Y

2

+

+

71

M

43

8

2.8

N

0

72

M

16

3

13.1

Y

1

+

+

73

M

45

9

52.3

Y

2

+

+

74

M

69

14

105.0

N

0

75

M

38

24

13.9

Y

1

+

+

76

M

66

20

8.7

N

0

77

M

55

9

32.1

Y

1

-

+

78

M

34

15

2.3

N

0

79

F

70

13

2.3

Y

1

-

+

80

M

81

72

13.6

Y

2

+

+

81

M

42

48

3.2

N

0

82

M

64

9

28.5

Y

1

+

+

83

M

35

14

9.8

Y

1

+

+

84

M

22

9

4.5

N

0

85

M

42

24

40.8

Y

1

+

+

86

M

66

48

30.4

N

0

87

F

17

8

1.4

N

0

88

M

40

10

39.4

N

0

89

M

18

3

187.0

Y

4

+

+

90

F

58

5

7.8

N

0

91

M

40

9

2.5

N

0

92

M

73

12

26.1

N

0

Resultados

43

Continuation

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

93

M

65

12

7.0

Y

3

-

+

94

M

45

48

4.2

Y

1

-

+

95

M

58

2

2.0

Y

1

-

+

96

F

42

4

3.5

N

0

97

F

77

5

2.4

N

0

98

M

50

4

47.4

Y

1

+

+

99

M

60

9

6.4

N

0

100

F

65

6

1.7

Y

2

+

+

101

M

17

5

1.2

N

0

102

M

19

6

1.2

N

0

103

M

54

6

6.4

N

0

104

M

30

4

26.1

Y

4

+

+

105

M

71

24

9.1

N

0

106

M

61

48

5.1

N

0

107

M

81

3  

1.7

Y

1

-

+

108

M

50

18  

55.5

Y

2

+

+

109

M

37

18  

6.3

Y

1

+

+

110

M

59

12  

3.8

Y

1

+

+

111

F

82  

48  

1.9

N

0

112

M

34

24  

15.5

Y

2

+

+

113

M

55

1  

13.1

Y

3

+

+

114

M

65

24

2.2

Y

2

+

+

115

M

25  

6  

1.8

N

0

Resultados

44

Continuation

Age

Volume

CE

Patient

Sex

(Years)

Time (h)

(mL)

CE*

CES**

CE Artery***

Venous***

116

M

45

24  

75.6

Y

1

+

+

117

M

53

63  

5.7

N

0

118

M

71  

17

1.7  

Y

1  

+  

+

119

M

49  

72  

2.4  

N

0  

120

M

39  

12  

1.9  

N

0  

 

121

M

33  

4  

1.6  

Y

1  

-­‐    

+

F – female / M – male. N – No / Y – Yes. TIME – time between the trauma and the first CTA. VOLUME – volume of the hemorrhagic component of the TBC. *CE – Contrast extravasation. ** – CES: Contrast extravasation score. *** – Contrast extravasation detected on arterial (CE artery) or venous (CE venous) phases of computed tomography angiography (CTA).

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Legends

A

B

C

Fig. 1 – A 19-year-old man presented with head trauma after falling 4 meters. (A) Axial NCCT 3 hours after injury demonstrated explosion of the left frontal lobe. (B) Focus of contrast pooling within the traumatic brain contusion in the arterial phase of the CTA. (C) Focus of contrast extravasation more apparent in the venous phase of the CTA.

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A

B

C

Fig. 2 – A 52-year-old man presented with head trauma after falling 7 meters. (A) Axial NCCT obtained 3 hours after trauma showed a right temporal contusion. (B) Note small focus of contrast pooling within the contusion (arrow). (C) NCCT for the imaging follow-up showing expansion after 24 hours of trauma.

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References

1. Acosta, J.A., Yang, J.C., Winchell, R.J., Simons, R.K., Fortlage, D.A., HollingsworthFridlund, P., and Hoyt, D.B. (1998). Lethal injuries and time to death in a level I trauma center. J. Am. Coll. Surg. 186, 528-533. 2. Langlois, J.A., Rutland-Brown, W., and Wald, M.M. (2006). The epidemiology and impact of traumatic brain injury: a brief overview. J. Head Trauma Rehabil. 21, 375378. 3. Selassie, A.W., Zaloshnja, E., Langlois, J.A., Miller, T., Jones, P., and Steiner, C. (2008).

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hospitalization, United States, 2003. J. Head Trauma Rehabil. 23, 123-131. 4. Thurman, D.J., Alverson, C., Dunn, K.A., Guerrero, J., and Sniezek, J.E. (1999). Traumatic brain injury in the United States: A public health perspective. J. Head Trauma Rehabil. 14, 602-615. 5. Zaloshnja, E., Miller, T., Langlois, J.A., and Selassie, A.W. (2008). Prevalence of long-term disability from traumatic brain injury in the civilian population of the United States, 2005. J. Head Trauma Rehabil. 23, 394-400. 6. Kurland, D., Hong, C., Aarabi, B., Gerzanich, V., and Simard, J.M. (2012). Hemorrhagic progression of a contusion after traumatic brain injury: a review. J. Neurotrauma 29, 19-31. 7. Alahmadi, H., Vachhrajani, S., and Cusimano, M.D. (2010). The natural history of brain contusion: an analysis of radiological and clinical progression. J. Neurosurg. 112, 1139-1145. 8. Chang,

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period. Neurosurgery 58, 647-656. 9. Compagnone, C., d’Avella, D., Servadei, F., Angileri, F.F., Brambilla, G., Conti, C., Cristofori, L., Delfini, R., Denaro, L., Ducati, A., Gaini, S.M., Stefini, R., Tomei, G., Tagliaferri, F., Trincia, G., and Tomasello, F. (2009) Patients with moderate head injury: a prospective multicenter study of 315 patients. Neurosurgery 64, 690-696. 10. Oertel, M., Kelly, D.F., McArthur, D., Boscardin, W.J., Glenn, T.C., Lee, J.H., Gravori, T., Obukhov, D., McBride, D.Q., and Martin, N.A. (2002). Progressive hemorrhage after head trauma: predictors and consequences of the evolving injury. J. Neurosurg. 96, 109-116. 11. Narayan, R.K., Maas, A.I., Servadei, F., Skolnick, B.E., Tillinger, M.N., and Marshall, L.F. (2008). Progression of traumatic intracerebral hemorrhage: a prospective observational study. J. Neurotrauma 25, 629-639. 12. White, C.L., Griffith, S., and Caron, J.L. (2009). Early progression of traumatic cerebral contusions: characterization and risk factors. J. Trauma 67, 508-514. 13. Yadav, Y.R., Basoor, A., Jain, G., and Nelson, A. (2006). Expanding traumatic intracerebral contusion/hematoma. Neurol. India 54, 377-381. 14. Letourneau-Guillon, L., Huynh, T., Jakobovic, R., Milwid, R., Symons, S.P., and Aviv, R.I. (2013). Traumatic intracranial hematomas: prognostic value of contrast extravasation. Am. J. Neuroradiol. 34, 773-779. 15. Flint, A.C., Manley, G.T., Gean, A.D., Hemphill, J.C. III, and Rosenthal, G. (2008). Post-operative expansion of hemorrhagic contusions after unilateral decompressive hemicraniectomy in severe traumatic brain injury. J. Neurotrauma 25, 503-512. 16. Stein, S.C., Spettell, C., Young, G., and Ross, S.E. (1993). Delayed and progressive brain injury in closed-head trauma: radiological demonstration. Neurosurgery 32, 2530. Resultados

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17. Wada, R., Aviv, R.I., Fox, A.J., Sahlas, D.J., Gladstone, D.J., Tomlinson, G., and Symons, S.P. (2007). CT angiography "spot sign" predicts hematoma expansion in acute intracerebral hemorrhage. Stroke 38, 1257-1262. 18. Demchuk, A.M., Dowlatshahi, D., Rodriguez-Luna, D., Molina, C.A., Blas, Y.S., Dzialowski, I., Kobayashi, A., Boulanger, J.M., Lum, C., Gubitz, G., Padma, V., Roy, J., Kase, C.S., Kosior, J., Bhatia, R., Tymchuk, S., Subramaniam, S., Gladstone, D.J., Hill, M.D., and Aviv, R.I. (2012). Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 11, 307-314. 19. Delgado-Almandoz, J.E., and Romero, J.M. (2011). Advanced CT imaging in the evaluation of hemorrhagic stroke. Neuroimag. Clin. N. Am. 21, 197-213. 20. Ederies, A., Demchuk, A., Chia, T., Gladstone, D.J., Dowlatshahi, D., BenDavit, G., Wong, K., Symons, S.P., and Aviv, R.I. (2009). Postcontrast CT extravasation is associated with hematoma expansion in CTA spot negative patients. Stroke 40, 1672-1676. 21. Li, N., Wang, Y., Wang, W., Ma, L., Xue, J., Weissenborn, K., Dengler, R., Worthmann, H., Wang, D.Z., Gao, P., Liu, L., Wang, Y., and Zhao, X. (2011). Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases. Stroke 42, 3441-3446. 22. Park, S.Y., Kong, M.H., Kim, J.H., Kang, D.S., Song, K.Y., and Huh, S.K. (2010). Role of 'Spot Sign' on CT Angiography to Predict Hematoma Expansion in Spontaneous Intracerebral Hemorrhage. J. Korean Neurosurg. Soc. 48, 399-405.

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23. Goldstein, J.N., Fazen, L.E., Snider, R., Schwab, K., Greenberg, S.M., Smith, E.E., Lev, M.H., and Rosand, J. (2007). Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology 68, 889-894. 24. Rosa Júnior, M., Rocha, A.J., Saade, N., Maia Júnior, A.C.M., and Gagliardi, R.J. (2013). Active extravasation of contrast within the hemorrhage (spot sign): a multidetector computed tomography finding that predicts growth and a worse prognosis in non-traumatic intracerebral hemorrhage. Arq. Neuropsiquiatr. 71, 791797. 25. Delgado-Almandoz, J.E., Kelly, H.R., Schaefer, P.W., Brouwers, H.B., Yoo, A.J., Stone, M.J., Goldstein, J.N., Rosand, J., Lev, M.H., Gonzalez, R.G., and Romero, J.M. (2012). CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage. J. Neurointerv. Surg. 4, 442-447. 26. Rosa Júnior, M., da Rocha, A.J., Maia Júnior, A.C.M., Saade, N., and Gagliardi, R.J. (2015). The active extravasation of contrast (spot sign) depicted on multidetector computed tomography angiography might predict structural vascular etiology and mortality in secondary intracranial hemorrhage. J. Comput. Assist. Tomogr. 39,217221. 27. Huang, A.P., Lee, C.W., Hsieh, H.J., Yang, C.C., Tsai, Y.H., Tsuang, F.Y., Kuo, L.T., Chen, Y.S., Tu, Y.K., Huang, S.J., Liu, H.M., and Tsai, J.C. (2011). Early parenchymal contrast extravasation predicts subsequent hemorrhage progression, clinical deterioration, and need for surgery in patients with traumatic cerebral contusion. J. Trauma 71, 1593-1599. 28. Mauser, H.W., van Nieuwenhuizen, O., and Veiga-Pires, J.A. (1984). Is contrastenhanced CT indicated in acute head injury? Neuroradiology 26, 31-32.

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29. Bullock, M.R., Chesnut, R., Ghajar, J., Gordon, D., Hartl, R., Newell, D.W., Servadei, F., Walters, B.C., and Wilberge, J. (2006). Surgical management of traumatic parenchymal lesions. Neurosurgery 58, S25-46. 30. Delgado-Almandoz, J.E., Yoo, A.J., Stone, M.J., Schaefer, P.W., Oleinik, A., Brouwers, H.B., Goldstein, J.N., Rosand, J., Lev, M.H., Gonzalez, R.G., and Romero, J.M. (2010). The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke 41, 54-60. 31. Tomida, M., Muraki, M., Uemura, K., and Yamasaki, K. (1998). Postcontrast magnetic resonance imaging to predict progression of traumatic epidural and subdural hematomas in the acute stage. Neurosurgery 43, 66 – 70, discussion 70-71. 32. Takanashi, Y., and Shinonaga, M. (2001). Magnetic resonance imaging for surgical consideration of acute head injury. J. Clin. Neurosci. 8, 240-244. 33. Murai, Y., Ikeda, Y., Teramoto, A., and Tsuji, Y. (1998). Magnetic resonance imagingdocumented extravasation as an indicator of acute hypertensive intracerebral hemorrhage. J. Neurosurg. 88, 650-655. 34. Lustenberger, T., Talving, P., Kobayashi, L., Barmparas, G., In-aba, K., Lam, L., Branco, B.C., and Demetriades, D. (2010). Early coagulopathy after isolated severe traumatic brain injury: relationship with hypoperfusion challenged. J. Trauma 69, 1410-1414. 35. Harhangi, B.S., Kompanje, E.J., Leebeek, F.W., and Maas, A.I. (2008). Coagulation disorders after traumatic brain injury. Acta Neurochir. 150, 165-175. 36. Smith, J.S., Chang, E.F., Rosenthal, G., Meeker, M., von Koch, K.C., Manley, G.T., and Holland, M.C. (2007). The role of early follow-up computed tomography imaging in the management of traumatic brain injury patients with intracranial hemorrhage. J. Resultados

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Trauma 63, 75-82. 37. Allard, C.B., Scarpelini, S., Rhind, S.G., Baker, A.J., Shek, P.N., Tien, H., Fernando, M., Tremblay, L., Morrison, L.J., Pinto, R., and Rizoli, S.B. (2009). Abnormal coagulation tests are associated with progression of traumatic intracranial hemorrhage. J. Trauma 67, 959-967. 38. Perel, P., Roberts, I., Shakur, H., Thinkhamrop, B., Phuen-pathom, N., and Yutthakasemsunt, S. (2010). Haemostatic drugs for traumatic brain injury. Cochrane Database Syst. Rev. CD007877. 39. Dewan, Y., Komolafe, E.O., Mejía-Mantilla, J.H., Perel, P., Roberts, I., and Shakur, H. (2012). CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebocontrolled trial. Trials 21, 13-87. 40. Huttner, H.B., Steiner, T., Hartmann, M., Köhrmann, M., Juettler, E., Mueller, S., Wikner, J., Meyding-Lamade, U., Schramm, P., Schwab, S., and Schellinger, P.D. (2006). Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin-related intracerebral parenchymal hemorrhage. Stroke 37, 404408. 41. Divani, A.A., Majidi, S., Luo, X., Souslian, F.G., Zhang, J., Abosch, A., and Tummala, R.P. (2011). The ABCs of accurate volumetric measurement of cerebral hematoma. Stroke 42, 1569-1574.

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Seção: Articles – Article 2 Journal of Computer Assisted Tomography Decision

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Title: The active extravasation of contrast (spot sign) depicted on multidetector computed tomography angiography might predict structural vascular etiology and mortality in secondary intracranial hemorrhage.

Type of Manuscript: Original articles.

Authors: Marcos Rosa Júnior,1 Antônio José da Rocha,1 Antônio Carlos Martins Maia Júnior,1 Nelson Saade,2 Rubens José Gagliardi.3 1

– Section of Neuroradiology, Santa Casa de Misericórdia de São Paulo, São Paulo

SP, Brazil. 2

– Division of Neurosurgery, Santa Casa de Misericórdia de São Paulo, São Paulo

SP, Brazil. 3

– Division of Neurology, Santa Casa de Misericórdia de São Paulo, São Paulo SP,

Brazil. There is no conflict of interest to declare. There is no funding source.

Correspondence to: Marcos Rosa Júnior, MD Santa Casa de Misericórdia de São Paulo – Serviço de Diagnóstico por Imagem Rua Dr. Cesário Motta Junior 112, Vila Buarque, São Paulo – SP / Brazil Postal code: 01221-020 Phone: +55 11 21767323 Fax: +55 11 21767321 e-mail: [email protected] Resultados

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Abstract

Objective: Intracerebral hemorrhage (ICH) occurs in 10-15% of all strokes and is accompanied by high rates of mortality, disability and neurological sequelae. Our aim was to assess the presence and prognostic implications of the active extravasation of contrast within the hemorrhage (spot sign) in a series of patients with secondary ICH. Methods: We analysed 59 subjects who arrived at a tertiary hospital with secondary ICH and a brain parenchyma hemorrhage > 2.0 cm in any axis. Results: Spot sign was observed in 11 subjects, including 8 patients with saccular aneurysm, 1 with arteriovenous malformation (AVM), 1 with coagulation disorder and 1 with venous sinus thrombosis. A 37.5% mortality rate was documented in the spot sign-negative group, while the presence of this imaging finding was followed by an 81.8% inhospital mortality rate. Conclusions: Spot sign was correlated with vascular etiology and was predictor of mortality in our series of patients.

Keywords: spot sign, active extravasation of contrast, multidetector CT angiography, secondary intracerebral hemorrhage, mortality.

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Introduction

Intracerebral hemorrhage (ICH) occurs in approximately 10-15% of all strokes, and patients with ICH have a poorer prognosis than those with ischemic strokes. ICH is accompanied by high rates of mortality, disability and neurological sequelae.1,2 Primary ICH is usually caused by systemic arterial hypertension (SAH) or amyloid angiopathy (AA). However, several conditions other than SAH and AA can also promote ICH. These conditions are known as secondary hemorrhage and include arteriovenous malformation (AVM), aneurysm, venous thrombosis, arteriovenous fistula (AVF), vasculitis, brain tumours, thrombolytic therapy, coagulation disorders and drug abuse.2 In both primary and secondary ICH, several features have been described as predictors of functional outcome after ICH, including the hematoma volume on presentation, midline shift, infratentorial location, intraventricular extension, and hydrocephalus.3,4 The widespread availability, fast acquisition, and lower cost of multidetector computed tomography (MDCT) has made this technique the preferred method for detecting ICH and, more recently, has also allowed the prognoses of ICH patients to be assessed.4 Several MDCT studies have confirmed that expanding hematomas occur mainly in the first 3 hours after the stroke and that the presence of active extravasation of the contrast within the hemorrhage (spot sign) during computed tomography angiography (CTA) predicts a worse prognosis and expansion of the hematoma in primary ICH,4-9 and, more recently, predicts mortality in secondary ICH.10 Our main aim was to study the spot sign characteristics on CTA-source images (CTA-SI) and to estimate their relationship with mortality in a cohort of Resultados

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Brazilian patients with secondary ICH.

Materials and Methods

Patients

This current study is part of a larger study that uses MDCT techniques to evaluate acute strokes. This protocol has been separately reviewed and approved by the institutional review board and the local ethics committee. From August 2011 to May 2013, patients of any age or gender who presented with a brain parenchyma hemorrhage > 2.0 cm in any axis, as demonstrated on noncontrast computed tomography (NCCT), that during evolution have been diagnosed as secondary ICH, were considered to be eligible for the protocol. CTA with identical imaging parameters was performed within the first three days after the ictus event. Imaging and clinical follow-up were used to diagnose secondary ICH, and CTA, digital subtraction angiography (DSA), magnetic resonance imaging (MRI) or surgery was used to confirm the associated structural abnormalities. Informed consent was obtained from all subjects (signed personally or by their guardians). We excluded patients with contraindications to the intravenous iodine contrast agent, those who refused study participation, and those with examinations that were of poor quality or that contained technical artefacts. The clinical history and laboratory results were reviewed to establish an SAH diagnosis and to confirm coagulation disorders. Patients with primary and traumatic hemorrhage were not included in this study. All patients were monitored in the intensive care unit or emergency room and treated according to the current guidelines for ICH management.11 Resultados

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All imaging exams were conducted using a 64-slice CT scanner (Brilliance CT 64 Channel, Philips Medical, Eindhoven, North Brabant, The Netherlands), adding CTA to the previously requested low-dose NCCT. The CTA and NCCT examination have covered the whole head using 120 kilovolts (KV) and 185 milliamperes (mAs), a 450 mm field of view (FOV) and a pitch of 0.673. After a time delay of 20 seconds, the first acquisition (arterial phase of the CTA) was performed by injecting a total dose of 1.0 ml/kg iodine contrast at 4–6 ml/s into a dual-head power injector (Medrad, Warrendale, PA, USA) with 18-G i.v. access, generally in a peripheral vein. The additional acquisition (venous phase of the CTA) was obtained using identical parameters 60 seconds after beginning the contrast administration.

Imaging analysis

The imaging interpretation included analyses of the NCCT and CTA-SI and the maximum intensity projection (MIP) and three-dimensional (3D) post-processed views. All data were post-processed using commercially available software on a workstation (Extended Brilliance Workspace v3.5.0.2250, Philips Medical Systems Nederland B.V., PC Best, the Netherlands). All studies were evaluated in consensus by 2 neuroradiologists (AJR and MRJ) experienced in diagnosing ICH and interpreting CTA. A spot sign was considered to be present or absent on CTA-SI based on the following previously defined criteria proposed by Delgado-Almandoz:4 ≥ 1 foci of contrast pooling within a hemorrhage (of any size and morphology), discontinuous from normal or abnormal vasculature adjacent to the hemorrhage, and attenuation > 120 Hounsfield Units (UH). Resultados

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The hematoma volumes were calculated on the first NCCT scan by estimating the three major axes and then multiplying the result by 0.5. An extra-axial hemorrhage was not considered in the volume measurement.

Statistical analysis

A univariate analysis using either Fisher’s exact test or Student’s t-test was used to determine the relationship between clinical and CT parameters and the presence of the spot sign and in-hospital mortality. We also used multivariate logistic regression analysis to identify the independent predictors of the presence of the spot sign and in-hospital mortality, and p < 0.05 was considered to be statistically significant.

Results

According to the inclusion criteria, 80 subjects were consecutively selected during the defined period. A total of 21 patients (21/80 – 26.2%) were subsequently excluded as follows: 15 subjects (15/80 – 18.7%) because of the impossibility of obtaining CTA images through a peripheral venous access and 6 subjects (6/80 – 7.5%) because of the inappropriate technical parameters used or presence of artefacts that hampered the analysis. A total of 59 subjects (59/80 – 73.8%) diagnosed with secondary ICH were enrolled in the study. The abnormalities that were ultimately diagnosed as ICHcausative are shown in Supplemental Digital Content. Demographic data, ICH volume and the elapsed time between the stroke and the first CTA were all analysed. Resultados

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The ICH etiology in our cohort was as follows: saccular aneurysm in 31 patients (31/59 – 52.5%), AVM in 3 patients (3/59 – 5.1%), AVF in 1 patient (1/59 – 1.7%), cavernous angioma in 2 patients (2/59 – 3.4%), primary glial tumour in 2 patients (2/59 – 3.4%), brain metastasis in 3 patients (3/59 – 5.1%), coagulation disorder in 8 patients (8/59 – 13.5%), ischemic stroke with hemorrhage in 4 patients (4/59 – 6.8%), moyamoya disease in 1 patient (1/59 – 1.7%), dural venous sinus thrombosis in 3 patients (3/59 – 5.1%) and a ruptured dermoid cyst with brain hemorrhage in 1 patient (1/59 – 1.7%). The mean hemorrhage volume was estimated as 28.7 ml (range, 1 – 158 ml). The mean hemorrhage volume was 46.7 ml in the spot sign-positive group (range, 2.6 – 158 ml) and 24.5 ml in the spot sign-negative group (range, 1 – 92.4 ml). A spot sign on CTA-SI was documented in 11 subjects (11/59 – 18.6%), including 8 patients with saccular aneurysm, 1 with parenchymal AVM, 1 with coagulation disorder and another 1 with venous sinus thrombosis (table 1). All spot signs (11/11 – 100%) were detected during the venous phase of the CTA in our series of patients. Conversely, this sign was only detected in 6 subjects during the arterial phase of the CTA (6/11 – 54.5%). Spot signs were documented up to 72 hours after the ictus event, with a mean of 17.4 hours (range, 1 – 72 hours) and a median of 6 hours (interquartile range [IQR], 1 –12 hours). From the ictus event to the CTA scan in our series, the overall median time was 10 hours (IQR, 6 – 24 hours), and the mean was 19.3 hours (range, 1 – 72 hours). Among the 11 spot signs documented in our series, 4 spot signs (4 11 / 36.3%) occurred in patients who underwent CT within 4 hours of the ictus, 3 (3 11 / 27.3%) in those examined between 4 and 8 hours, 2 (2 - 11 / 18.2%) others

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between 9 and 12 hours and additionally 2 (2 - 11 / 18.2%) spot signs in patients who underwent CT with over 12 hours of the ictus. A 37.5% mortality rate (18/48) was documented in the spot sign-negative group, while the presence of this imaging finding was associated with an in-hospital mortality rate of 81.8% (9/11) (p = 0.006) (Figure 1 and 2). Table 2 summarises clinical and CTA predictors of a spot sign and mortality in our patient series. In our series, the variables that were most related to the presence of spot signs were an ictus event lasting < three hours, hemorrhage volume > 100 ml, and GCS ≤ 8 (all variables with p < 0.05). The variables that most influenced mortality were the presence of a spot sign (even when considered alone), an age older than 70 years, blood glucose > 170 mg/dl, associated history of arterial hypertension, hemorrhage volume > 100 ml, and GCS ≤ 8 (all variables with p < 0.05). However, in the multivariate analysis, the factors that most influenced mortality were an age older than 70 years old and GCS ≤ 8.

Discussion

The active extravasation of contrast within a hemorrhage has been described in catheter angiography for nearly 30 years.12 Several studies have also demonstrated its occurrence in CTA.3-9 However, the use of CTA to evaluate secondary ICH has been demonstrated only recently. Our results align with those of a previous report, confirming that ICH is associated with higher mortality.10 Likewise, our current data highlighted the occurrence of spot signs on CTA-SI in secondary ICH as a predictor of mortality in univariate analysis, similar to the results of another recent report.10 Our results also highlighted that the occurrence of spot signs in our Resultados

62

series predicted mortality in 81.8% of patients, a higher rate than that previously reported (72%).10 Ethnic and environmental influences on secondary ICH prognosis remain as possible arguments to explain the poor outcomes in this series of Brazilian patients. Our data reinforce the use of CTA-SI in vivo to evaluate some peculiarities between different populations. The association between spot sign and in-hospital mortality observed in univariate analysis was not found in the multivariate logistic regression model. Instead, the predictors of in-hospital mortality in the multivariate logistic regression in our cohort were age > 70 years old and GCS ≤ 8. DelgadoAlmandoz et al.10 suggest that the effect of the spot sign on in-hospital mortality might be mediated in combination with the admission GCS score; spot signs may indicate those patients with more damage to the blood-brain barrier or greater neuronal injury, which manifests as a lower GCS score. Although Delgado-Almandoz et al.10 did not find any statistical significance between the GCS score and the presence of a spot sign, our study found a statistically significant correlation between low GCS values and the presence of spot signs, which might corroborate this hypothesis. However, more studies are needed to clarify this possible association. Brouwers et al.13 recently showed that spot signs did not predict mortality in a series of patients with aneurysms. Early surgical intervention and possible knowledge bias imposed by the CTA results might not have been excluded in this study; these factors may have influenced their patients’ treatments and prognoses.13 We believe that the occurrence of spot signs on secondary ICH should not be neglected, even when an aneurysm is observed. Further studies that include CTA results should be encouraged to investigate how this imaging finding affects the etiology of ICH.

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Despite the seemingly lower frequency of spot signs in secondary ICH compared to primary ICH, which varies from 19 to 56%,3-7,9 the current criteria for identifying this sign on CTA-SI are similar.4,10 Our series confirmed the lower frequency of spot signs in secondary ICH (18.6%). Furthermore, our data align with previously published results by Delgado-Almandoz et al.10 (14.5%) and Brouwers et al.13 (14%). Our data confirmed that contrast extravasation in secondary ICH is an early and uncommon event that might be documented in CTA-SI. However, contrast extravasation is not necessarily restricted to the first three hours after the ictus event; in our patient cohort, it occurred up to seventy-two hours after the ictus event. The relationship between late detected spot signs and mortality might be observed in our patients with predominantly vascular structural abnormalities, but this finding requires further confirmation in larger studies. The use of CTA was relevant in evaluating our patients with secondary ICH, particularly to confirm the etiology of bleeding during the first imaging examination when vascular abnormalities were present. Several studies have shown that CTA is a robust tool to demonstrate vascular structural abnormalities, indicating a need for surgical procedures even in the absence of DSA. However, conventional angiography is still necessary either in doubtful cases or in cases of negative MDCTAs with strong clinical suspicions.14,15 Vascular structural abnormalities in the presence of spot signs on CTA-SI were more commonly aneurysms (8/31 – 25.8%) than AVM (1/3 – 33%) or venous sinus thrombosis (1/3 – 33%). The strong association between the occurrence of a spot sign and structural vascular etiology is also useful for strengthening the Resultados

64

differential diagnosis of vascular structural aetiology when a secondary ICH has been suspected, thus, increasing the scope of interpreting this finding for diagnostic purposes. Spot sign is a strong predictor of expansion of the primary ICH, however, its pathology and exact relationship to the hematoma is unclear.16,17 Intuitively, spot sign are frequently thought to represent the site of vessel rupture and active bleeding in primary ICH.18 The higher frequency of spot sign and the increase of ICH dimensions were demonstrated to be correlated in the venous phase of CT angiography to corroborate this hypothesis.17 Dowlatshahi et al.16 have postulated that spot signs had different pathological characteristics depending on when they are imaged in relation to the onset of the primary hemorrhage. In the early phase of ICH, spot sign was a site of rupture and active extravasation of iodinated contrast, whereas in later phases, it represented a point of resolved hemorrhage after physiological hemostasis or tamponade from rising intracranial pressures.16 Delgado-Almandoz et al.10 have corroborated this hypothesis of injury to the vascular wall. We argue that the occurrence of the spot sign in patients with vascular etiology in our study is in line with this argument. However further larger study remains needed to confirm this hypothesis. Despite these results, a number of spot sign mimics are attributed to vascular causes, such as aneurysms and AVMs (they are easily recognised by their continuity with adjacent vessels). There are also non-vascular causes that can mimic spot signs on CTA-SI, including heterogeneous bleeding and foci of calcification. These findings should all be scrutinised by both NCCT and CTA to avoid misdiagnosing spot signs.19 Our report has certain limitations, including the delayed arrival of the patients to our centre, as well as the small sample size of patients, which limits the multivariate statistical analysis. As control imaging examinations were often Resultados

65

unavailable because of the usual practice of quickly treating ICH, imaging evaluations of the spot signs to predict hematoma expansions were not possible. The authors encourage the use of this standardised MDCT protocol, including both arterial (earlier) and venous (later) CTA phases, in imaging studies for ICH when secondary causes of hemorrhage are suspected, even among patients who arrive at the hospital later than three hours after the ictus event. CTA-SI has been shown to be useful in detecting spot signs, which have been positively associated with structural vascular abnormalities that cause ICH (exempting the performance of DSA). In conclusion the occurrence of spot signs on CTA-SI determined increased mortality in our cohort of Brazilian patients with secondary ICH. Spot signs also allowed us to suspect vascular structural etiology using the minimally invasive CTA technique. Further imaging studies of this topic are needed, particularly to define etiologic diagnoses and to better comprehend the prognosis of secondary ICH.

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Table 1 – Demographic and clinical patient data, with the presence of the spot sign. SPOT AGE

VOLUME

SIGN

PATIENT

Sex

(years)

ICTUS (H)

(ml)

(+ / -)

DIAGNOSIS**

SS ARTERY*** SS VENOUS

1

F

70

1

158.0

+

1

-

+

2

F

46

12

2.6

+

1

+

+

3

M

38

6

140.0

+

3

+

+

4

M

63

1

49.0

+

1

-

+

5

M

43

4

16.0

+

12

-

+

6

F

83

3

9.9

+

1

-

+

7

F

62

8

11.3

+

1

+

+

8

F

41

72

17.0

+

1

+

+

9

M

62

72

3.4

+

1

+

+

10

F

95

1

25.0

+

1

-

+

11

F

77

12

82.0

+

8

-

+

F – female / M – male ** - Diagnosis - 1 - aneurysm; 2 - mycotic aneurysm; 3 - arteriovenous malformation (AVM); 4 - arteriovenous fistula (AVF); 5 - cavernoma; 6 - primary neoplasm; 7 - metastasis; 8 coagulation disorder; 9 - ischemic stroke with hemorrhage; 10 - ruptured dermoid cyst with brain hemorrhage; 11 - moyamoya; 12 - dural venous sinus thrombosis. *** - Spot Sign detected on arterial (SS artery) or venous (SS venous) phases of computed tomography angiography

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Table 2 - Clinical and CTA predictors of spot signs and mortality in our patient series. Spot Sign, n (%)

p Value*

In-hospital mortality, n (%)

p Value*

11 (18.6)

NA

27 (45.7)

NA

Male (n=24)

4 (17)

0.74

8 (33)

0.18

Female (n=35)

7 (20)

19 (54)

≤45 (n=15)

3 (20)

4 (27)

46-70 (n=35)

5(14)

71-95 (n=9)

3(33)

6 (67)

≤3 (n=8)

4 (50)

6 (75)

>3 - ≤6 (n=13)

2(15)

>6, n=38

5(13)

All patients (n=59)

Sex

Age (years)

0.41

17 (49)

0.002x

Time from ictus (hours)

0.04

6 (46)

0.23

15 (39)

Blood glucose ≥ 170 mg/dl No (n=56)

11 (20)

Yes (n=3)

0 (0)

0.86

24 (43)

0.05

3 (100)

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68

Continuation

Spot Sign, n (%)

p Value*

In-hospital mortality, n (%)

p Value*

ICH site Lobar (n=48)

7 (15)

22 (46)

Deep gray matter (n=7)

3 (43)

Infratentorial (n=4)

1 (25)

2 (50)

≤20 (n=35)

6 (17)

16 (46)

>20 - ≤100 (n=22)

3 (14)

>100 (n=2)

2 (100)

2 (100)

Aneurysm (n=31)

8 (26)

16 (52)

AVM (n=3)

1 (33)

CD (n=8)

1 (13)

6 (75)

VT (n=3)

1 (33)

1 (33)

≤8 (n=20)

7 (35)

15 (75)

9-12 (n=12)

1 (8)

>13 (n=27)

3 (11)

0.15

3 (43)

1

ICH volume (ml)

0.03

9 (41)

0.04

Diagnosis

0.26

1 (33)

0.37

Admission GCS

0.008

5 (42)

0.001x

7 (26)

Blood hypertension >140x90 mmHg No (n=21)

2 (10)

Yes (n=38)

9 (24)

0.29

6 (29)

0.05

21 (55)

Resultados

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*Univariate analysis x - Multivariate logistic regression analysis for in-hospital mortality ICH - intracerebral hemorrhage GCS - Glasgow Coma Scale CD - Coagulation disorder VT - Venous thrombosis

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70

Supplemental Digital Content – The demographic and clinical data of our patient series. SPOT AGE

VOLUME

SIGN

PATIENT

Sex

(years)

ICTUS (H)

(ml)

(+ / -)

SSS*

DIAGNOSIS**

1

F

75

7

9.7

-

0

1

2

F

50

4

11.0

-

0

1

3

F

50

24

11.0

-

0

1

4

F

58

6

12.0

-

0

1

5

F

24

72

38.0

-

0

1

6

F

69

12

46.0

-

0

6

7

F

51

24

37.0

-

0

1

8

F

79

24

61.1

-

0

7

9

F

55

3

3.3

-

0

8

10

F

65

8

83.3

-

0

8

11

F

56

12

4.8

-

0

1

12

F

56

9

1.0

-

0

1

13

F

64

48

4.8

-

0

1

14

F

57

24

27.6

-

0

1

15

F

70

1

158.0

+

3

1

16

F

35

8

2.7

-

0

5

17

F

64

12

13.0

-

0

8

18

F

66

72

4.8

-

0

1

19

F

54

12

49.0

-

0

1

20

F

46

12

2.6

+

1

1

21

F

69

6

13.5

-

0

8

SS ARTERY*** SS VENOUS

-

+

+

+

Resultados

71

Continuation SPOT AGE

VOLUME

SIGN

PATIENT

Sex

(years)

ICTUS (H)

(ml)

(+ / -)

SSS*

DIAGNOSIS**

22

F

67

5

18.0

-

0

1

23

F

43

5

1.0

-

0

12

24

F

64

12

20.0

-

0

11

25

F

2

4

48.0

-

0

3

26

M

38

6

140.0

+

3

3

27

M

40

8

70.0

-

0

2

28

M

55

72

13.5

-

0

4

29

M

81

72

38.0

-

0

7

30

M

52

3

10.8

-

0

6

31

M

28

24

15.0

-

0

5

32

M

72

24

80.0

-

0

3

33

M

61

7

9.5

-

0

8

34

M

62

6

92.4

-

0

9

35

M

42

3

43.4

-

0

8

36

M

30

6

65.0

-

0

1

37

M

57

24

2.5

-

0

10

38

M

67

6

9.5

-

0

7

39

M

49

14

11.4

-

0

1

40

M

44

10

1.0

-

0

9

41

M

77

6

24.0

-

0

9

42

M

63

1

49.0

+

1

1

43

M

25

10

34.0

-

0

1

SS ARTERY*** SS VENOUS

+

+

-

+

Resultados

72

Continuation SPOT AGE

VOLUME

SIGN

PATIENT

Sex

(years)

ICTUS (H)

(ml)

(+ / -)

SSS*

DIAGNOSIS**

SS ARTERY*** SS VENOUS

44

M

43

4

16.0

+

1

12

-

+

45

F

83

3

9.9

+

2

1

-

+

46

F

50

48

26.7

-

0

1

47

F

62

8

11.3

+

1

1

+

+

48

F

41

72

17.0

+

1

1

+

+

49

M

61

72

4.7

-

0

1

50

F

74

8

15.0

-

0

9

51

M

62

72

3.4

+

1

1

+

+

52

M

59

24

4.4

-

0

1

53

F

61

4

1.7

-

0

1

54

F

95

1

25.0

+

2

1

-

+

55

F

34

24

2.2

-

0

12

56

F

77

12

82.0

+

3

8

-

+

57

M

19

2

28.0

-

0

8

58

F

51

48

4.7

-

0

1

59

M

54

10

50.5

-

0

1

F - female / M - male * - SSS: spot sign score ** - Diagnosis - 1 - aneurysm; 2 - mycotic aneurysm; 3 - arteriovenous malformation (AVM); 4 arteriovenous fistula (AVF); 5 - cavernoma; 6 - primary neoplasm; 7 - metastasis; 8 - coagulation disorder; 9 - ischemic stroke with hemorrhage; 10 - ruptured dermoid cyst with brain hemorrhage; 11 moyamoya; 12 - dural venous sinus thrombosis. *** - Spot Sign detected on arterial (SS artery) or venous (SS venous) phases of computed tomography angiography. Resultados

73

A

B

Figure 1. A 70-year-old woman presented with a sudden headache and decreased level of consciousness. (A) NCCT showed a right frontotemporal ICH. (B) Coronal MIP image of CTA showed a saccular aneurysm in the right middle cerebral artery and a small focus of contrast pooling within the ICH (arrow). The patient died after the CTA examination.

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74

A

B

Figure 2. A 38-year-old man presented with a sudden headache and a decreased level of consciousness. (A) Coronal MIP image of CTA showing the AVM nidus, with adjacent hemorrhage. (B) A small focus of contrast pooling within the ICH (arrow). The patient died 24 hours after the CTA examination.

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References

1.

Fischbein NJ, Wijman CA. Nontraumatic intracranial hemorrhage. Neuroimag Clin N Am. 2010;20:469-492.

2.

Siddiqui FM, Bekker SV, Qureshi AI. Neuroimaging of hemorrhage and vascular defects. Neurotherapeutics. 2011;8:28-38.

3.

Wada R, Aviv RI, Fox AJ, et al. CT angiography "spot sign" predicts hematoma

expansion

in

acute

intracerebral

hemorrhage.

Stroke.

2007;38:1257-1262.

4.

Delgado Almandoz JE, Romero JM. Advanced CT imaging in the evaluation of hemorrhagic stroke. Neuroimag Clin N Am. 2011;21:197-213.

5.

Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol. 2012;11:307-314.

6.

Delgado Almandoz JE, Yoo AJ, Stone MJ, et al. Systematic characterization of the computed tomography angiography spot sign in primary intracerebral

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hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score. Stroke. 2009;40:2994-3000.

7.

Hallevi H, Abraham AT, Barreto AD, et al. The spot sign in intracerebral hemorrhage: the importance of looking for contrast extravasation. Cerebrovasc Dis. 2010;29:217-220.

8.

Brouwers HB, Greenberg SM. Hematoma expansion following acute intracerebral hemorrhage. Cerebrovasc Dis. 2013;35:195-201.

9.

Rizos T, Dörner N, Jenetzky E, et al. Spot signs in intracerebral hemorrhage: useful for identifying patients at risk for hematoma enlargement? Cerebrovasc Dis. 2013;35:582-589.

10.

Delgado Almandoz JE, Kelly HR, Schaefer PW, et al. CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage. J Neurointervent Surg. 2012;4:442-447.

11.

Morgenstern LB, Hemphill JC 3rd, Anderson C, et al. Guidelines for the Management of Spontaneous Intracerebral Hemorrhage: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke. 2010;41:2108-2129.

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12.

Kowada M, Yamaguchi K, Matsuoka S, et al. Extravasation of angiographic contrast material in hypertensive intracerebral hemorrhage. J Neurosurg. 1972;36:471-473.

13.

Brouwers HB, Backes D, Kimberly WT, et al. Computed tomography angiography spot sign does not predict case fatality in aneurysmal subarachnoid hemorrhage with

intraparenchymal

extension.

Stroke.

2013;44:1590-1594. 14.

Millon D, Derelle AL, Omoumi P, et al. Nontraumatic Subarachnoid Hemorrhage Management: Evaluation with Reduced Iodine Volume at CT Angiography. Radiology. 2012;264:203-209.

15.

Pozzi-Mucelli F, Bruni S, Doddi M, et al. Detection of intracranial aneurysms with 64 channel multidetector row computed tomography: Comparison with digital subtraction angiography. Eur J Radiol. 2007;64:15-26.

16.

Dowlatshahi D, Wasserman JK, Momoli F, et al. Evolution of Computed Tomography Angiography Spot Sign Is Consistent With a Site of Active Hemorrhage in Acute Intracerebral Hemorrhage. Stroke. 2014;45:277-280.

17.

Rosa Júnior M, Rocha AJ, Saade N, et al. Active extravasation of contrast within the hemorrhage (spot sign): a multidetector computed tomography finding that

predicts growth and a worse prognosis in non-traumatic

intracerebral hemorrhage. Arq Neuropsiquiatr. 2013;71:791-797.

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18.

Goldstein JN, Fazen LE, Snider R, et al. Contrast extravasation on CT angiography predicts hematoma expansion in intracerebral hemorrhage. Neurology. 2007;68:889-894.

19.

Gazzola S, Aviv RI, Gladstone DJ, et al. Vascular and nonvascular mimics of the CT angiography "spot sign" in patients with secondary intracerebral hemorrhage. Stroke. 2008; 39:1177-1183.

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5. CONSIDERAÇÕES FINAIS

80

Os resultados dos nossos estudos confirmaram a associação entre a presença do extravasamento do contraste no interior das contusões cerebrais traumáticas e a expansão de seu componente hemorrágico, o pior prognóstico e a maior letalidade neste grupo de pacientes. Nossos resultados confirmaram também, a associação entre a presença do spot sign e a maior letalidade em pacientes com HIPC de causa secundária. Nossos trabalhos enfatizaram a importância do uso da ângio-TCMD no cenário das HIPC, tanto de causa traumática quanto de causa secundária. É possível com essa importante ferramenta detectar no primeiro estudo de imagem a provável causa secundária da HIPC, como também estratificar o risco maior de morte no exame de entrada no hospital. Já em relação as contusões cerebrais traumáticas podemos ir além, ao predizer o risco de expansão do componente hemorrágico da contusão no primeiro exame do paciente. Enfatizamos ainda a ocorrência tardia do spot sign nestes dois grupos de pacientes, em que encontramos este sinal em até 72 horas após o icto e não apenas nas primeiras horas. Nossos estudos ressaltaram a necessidade de priorizar o atendimento rápido da HIPC, tornando seu diagnóstico mais precoce e eficiente e reforçando a necessidade de instituição de políticas específicas que agilizem o atendimento e permitam influir nos fatores prognósticos, reduzindo a letalidade desta grave e frequente afecção neurológica. Nossos resultados nos permitiram sugerir a supressão da fase arterial da ângio-TCMD no cenário do trauma, caso não haja suspeita clínica de lesão arterial, pois foi a fase venosa da ângio-TCMD a mais importante para detecção do spot sign neste grupo de pacientes. Já em relação as HIPC secundárias não é possível Considerações Finais

81

dispensar a fase arterial da ângio-TCMD, pois na chegada do paciente à TC ainda não se sabe qual a causa da hemorragia, portanto é possível que seja uma causa arterial e a ângio-TCMD deve ser realizada com todas as fases (arterial e venosa). Recomendamos, portanto, o uso da ângio-TCMD nas fases arterial e venosa nos pacientes com HIPC não traumática e apenas da fase venosa nos pacientes com TCE que apresentem contusões cerebrais hemorrágicas, pois nossos trabalhos enfatizam a importância do método na detecção das causas secundárias de HIPC, bem como na avaliação do prognóstico e do risco de expansão da hemorragia nestes grupos de pacientes. Como perspectivas futuras esse estudo é importante, pois permite sedimentar o conhecimento específico de uma técnica nova, além de reconhecer as particularidades

do

nosso

atendimento

médico

de

urgência

e

algumas

peculiaridades da nossa população, vislumbrando a possibilidade de intervenção com políticas objetivas. Dentre elas destaca-se a necessária definição de terapêutica específica, particularmente a proposta de estudos prospectivos relacionando o uso de drogas hemostáticas, como o fator VII ativado e o ácido ε-aminocaproico (EACA) na tentativa de conter a expansão da HIPC, particularmente a traumática. Ressaltamos que ainda são escassos na literatura os estudos multicêntricos, randomizados usando estes medicamentos neste cenário particular, como já existem nas HIPC primárias, o que abre uma oportunidade de novas pesquisas sobre o tema.

Considerações Finais

82

6. REFERÊNCIAS BIBLIOGRÁFICAS

83

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Delgado-Almandoz JE, Kelly HR, Schaefer PW, Brouwers HB, Yoo AJ, Stone MJ, et al. CT angiography spot sign predicts in-hospital mortality in patients with secondary intracerebral hemorrhage. J Neurointerv Surg 2012;4:442-447. Delgado-Almandoz JE and Romero JM. Advanced CT imaging in the evaluation of hemorrhagic stroke. Neuroimag Clin N Am 2011;21:197-213. Delgado Almandoz JE, Yoo AJ, Stone MJ, Schaefer PW, Goldstein JN, Rosand J, et al. Systematic characterization of the computed tomography angiography spot sign in primary intracerebral hemorrhage identifies patients at highest risk for hematoma expansion: the spot sign score. Stroke 2009;40:2994-3000. Delgado Almandoz JE, Yoo AJ, Stone MJ, Schaefer PW, Oleinik A, Brouwers HB, et al. The spot sign score in primary intracerebral hemorrhage identifies patients at highest risk of in-hospital mortality and poor outcome among survivors. Stroke 2010;41:54–60. Demchuk AM, Dowlatshahi D, Rodriguez-Luna D, Molina CA, Blas YS, Dzialowski I, et al. Prediction of haematoma growth and outcome in patients with intracerebral haemorrhage using the CT-angiography spot sign (PREDICT): a prospective observational study. Lancet Neurol 2012;11:307-314. Dewan Y, Komolafe EO, Mejía-Mantilla JH, Perel P, Roberts I and Shakur H. (2012). CRASH-3 - tranexamic acid for the treatment of significant traumatic brain injury: study protocol for an international randomized, double-blind, placebo-controlled trial. Trials 2012;21:13–87. Divani AA, Majidi S, Luo X, Souslian FG, Zhang J, Abosch A, et al. The ABCs of accurate volumetric measurement of cerebral hematoma. Stroke 2011;42:1569– 1574.

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Intracerebral Hemorrhage. Stroke 2014;45:277-280.

Ederies A, Demchuk A, Chia T, Gladstone DJ, Dowlatshahi D, BenDavit G, et al. Postcontrast CT extravasation is associated with hematoma expansion in CTA spot negative patients. Stroke 2009;40:1672–1676. Fischbein NJ, Wijman CA. Nontraumatic intracranial hemorrhage. Neuroimag Clin N Am 2010;20:469-492. Fisher CM. Cerebral miliary aneurysms in hypertension. Am J Pathol 1972;66:313– 330. Flint AC, Manley GT, Gean AD, Hemphill JC III and Rosenthal G. Post-operative expansion

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Huang AP, Lee CW, Hsieh HJ, Yang CC, Tsai YH, Tsuang FY, et al. Early parenchymal contrast extravasation predicts subsequent hemorrhage progression, clinical deterioration, and need for surgery in patients with traumatic cerebral contusion. J Trauma 2011;71:1593-1599. Huttner HB, Steiner T, Hartmann M, Köhrmann M, Juettler E, Mueller S, et al. Comparison of ABC/2 estimation technique to computer-assisted planimetric analysis in warfarin-related intracerebral parenchymal hemorrhage. Stroke 2006;37:404–408. Kowada M, Yamaguchi K, Matsuoka S, Ito Z. Extravasation of angiographic contrast material in hypertensive intracerebral hemorrhage. J Neurosurg 1972;36:471-473. Kurland D, Hong C, Aarabi B, Gerzanich V and Simard JM. Hemorrhagic progression of a contusion after traumatic brain injury: a review. J Neurotrauma 2012;29:19-31. Langlois JA, Rutland-Brown W and Wald MM. The epidemiology and impact of traumatic brain injury: a brief overview. J. Head Trauma Rehabil 2006;21:375–378. Letourneau-Guillon L, Huynh T, Jakobovic R, Milwid R, Symons SP and Aviv RI. Traumatic intracranial hematomas: prognostic value of contrast extravasation. Am J Neuroradiol 2013;34:773-779. Li N, Wang Y, Wang W, Ma L, Xue J, Weissenborn K, et al. Contrast extravasation on computed tomography angiography predicts clinical outcome in primary intracerebral hemorrhage: a prospective study of 139 cases. Stroke 2011;42:34413446. Lustenberger T, Talving P, Kobayashi L, Barmparas G, In-aba K, Lam L, et al. Early coagulopathy after isolated severe traumatic brain injury: relationship with hypoperfusion challenged. J Trauma 2010;69:1410–1414. Mauser HW, van Nieuwenhuizen O and Veiga-Pires JA. Is contrast-enhanced CT indicated in acute head injury? Neuroradiology 1984;26:31–32. Referências Bibliográficas

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for

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From

the

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P,

Roberts

I,

Shakur

H,

Thinkhamrop

B,

Phuen-pathom

N

and

Yutthakasemsunt S. Haemostatic drugs for traumatic brain injury. Cochrane Database Syst Rev. 2010 CD007877. Pontes-Neto OM, Oliveira-Filho J, Valiente R, Friedrich M, Pedreira B, Rodrigues BC, et al. Brazilian guidelines for the manegement of intracerebral hemorrhage. Arq Neuropsiquiatr 2009;67:940-950. Pozzi-Mucelli F, Bruni S, Doddi M, Calgaro A, Braini M, Cova M. Detection of intracranial aneurysms with 64 channel multidetector row computed tomography: Comparison with digital subtraction angiography. Eur J Radiol 2007;64:15-26. Rosa Júnior M, Rocha AJ, Saade N, Maia Júnior AC and Gagliardi RJ. Active extravasation of contrast within the hemorrhage (spot sign): a multidetector computed tomography finding that predicts growth and a worse prognosis in nontraumatic intracerebral hemorrhage. Arq Neuropsiquiatr 2013;71:791-797. Rosa Júnior M, da Rocha AJ, Saade N, Maia Júnior AC and Gagliardi RJ. The active extravasation of contrast (spot sign) depicted on multidetector computed tomography angiography might predict structural vascular etiology and mortality in secondary intracranial hemorrhage. J Comput Assist Tomogr 2015;39:217-221. Rosa Júnior M. Spot sign como fator preditor de crescimento e implicações prognósticas nas hemorragias intraparenquimatosas cerebrais não traumáticas. Tese (Mestrado). São Paulo: Faculdade de Ciências Médicas da Santa Casa de São Paulo; 2013. Rizos T, Dörner N, Jenetzky E, Sykora M, Mundiyanapurath S, Horstmann S, et al. Spot signs in intracerebral hemorrhage: useful for identifying patients at risk for hematoma enlargement? Cerebrovasc Dis 2013;35:582-589. Selassie AW, Zaloshnja E, Langlois JA, Miller T, Jones P and Steiner C. Incidence of long-term disability following traumatic brain injury hospitalization, United States, 2003. J Head Trauma Rehabil 2008;23:123–131. Referências Bibliográficas

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7. ANEXOS

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ANEXO 1 APROVAÇÃO COMITÊ DE ÉTICA

Anexos

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ANEXO 2 TERMO DE CONSENTIMENTO LIVRE E ESCLARECIDO Prezado paciente, Você está sendo convidado a participar de um estudo realizado no Hospital da Santa Casa de Misericórdia de São Paulo. Ele será conduzido sob a responsabilidade do investigador dessa instituição, Dr. Marcos Rosa Júnior (médico assistente do Serviço de Diagnóstico por Imagem da Santa Casa, CRM 131639). Antes de decidir se irá participar desse trabalho, é importante que você entenda por que essa pesquisa está sendo realizada e como será seu envolvimento. O título dessa

pesquisa

é

“Fatores

preditores

de

crescimento

da

hemorragia

intraparenquimatosa encefálica na avaliação por angiotomografia multidetectores”, que tem como objetivo avaliar, através da tomografia computadorizada, achados que possam predizer que a hemorragia cerebral pode crescer ainda mais, e desta forma permitindo um tratamento mais eficaz e rápido para os pacientes. É importante dizer que o exame que será realizado (angiotomografia) já está bem estabelecido na área médica há muitos anos e é realizado de forma rotineira em todo mundo e este exame já faz parte da conduta habitual para o seu atendimento, usado na rotina do hospital e o estudo usará apenas os dados desse exame e do prontuário médico para avaliar a evolução clínica do paciente, visando melhorar o diagnóstico e a conduta médica. A tomografia é um exame radiológico de alta resolução, que permite uma acurada avaliação do cérebro, usando raios X em doses bem estabelecidas e não causam sofrimento, nem risco adicional à saúde. Será necessário usar contraste iodado que será injetado em uma veia periférica, para se estudar os vasos do cérebro. Este contraste já é usado há muitos anos em todo mundo, em doses bem estabelecidas, cujas eventuais reações são raras e ocorrem na minoria dos pacientes, sendo que a maioria dos pacientes não apresenta estas reações. Porém, alguns pacientes podem apresentar

uma reação leve à

administração do meio de contraste iodado caracterizada por uma irritação na garganta ou espirros, calor transitório e coceira no corpo, inchaço nos olhos, náuseas e vômitos; uma parcela menor ainda de pacientes (cerca de 1 caso a cada 1000 pacientes) pode apresentar uma reação mais grave, caracterizada por dificuldades para respirar, choque, insuficiência renal e problemas cardiovasculares; e as complicações fatais ao uso do meio de contraste iodado são extremamente raras (cerca de 1 caso em 400.000 pacientes). Estou ciente que a equipe médica e Anexos

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de enfermagem desta instituição está apta a tratar qualquer tipo de reação apresentada pelo paciente. Caso este estudo confirme as expectativas, poderá ser utilizado em vários outros hospitais, com o intuito de ajudar o tratamento de mais indivíduos. Cabe ao responsável permitir ou não a participação do paciente neste estudo. A participação é voluntária, sem ônus e sem remuneração e você pode retirar o consentimento quando quiser sem prejuízo ao seu atendimento. Vale lembrar que a angiotomografia habitualmente é feita nesses indivíduos com hemorragia cerebral. A permissão solicitada é apenas na inclusão dos dados do paciente no projeto de pesquisa. Se decidir em não participar, o paciente continuará a receber os cuidados médicos habituais. Se concordar em participar, o paciente fará o exame e seus dados e o resultado do exame permanecerão em absoluto sigilo. O pesquisador do estudo também fornecerá ao responsável quaisquer informações pertinentes durante ou após a realização do exame. As informações obtidas no estudo serão armazenadas e processadas para fins de avaliação científica. O Comitê de Ética em Pesquisa e a Comissão Nacional de Ética em Pesquisa terão permissão para examinar os seus dados de estudo e registros médicos a fim de verificar se o estudo está sendo realizado adequadamente e de que você deu seu total consentimento (todas essas pessoas estão sujeitas a um termo de sigilo). Se os resultados do estudo forem publicados, sua identidade será mantida em sigilo. Afirmo que fui convenientemente esclarecido pelo pesquisador e que entendi o que me foi explicado, de modo que concordo em participar da pesquisa de livre e espontânea vontade. São Paulo,___de____________de _____ .

____________________________ Nome do responsável por extenso

_____________________________ Assinatura

____________________________ Nome da testemunha por extenso

_____________________________ Assinatura

___________________________ Nome da testemunha por extenso

_____________________________ Assinatura

____________________________ Nome do pesquisador por extenso

_____________________________ Assinatura Anexos

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ANEXO 3 NORMAS DE PUBLICAÇÃO – Journal of Neurotrauma – Article 1

Instructions for Authors

The Journal of Neurotrauma publishes papers dealing with all aspects of neurotrauma. This includes the anatomy, biochemistry, biophysics, immunology, pathology, pharmacology, and physiology of brain, spinal, and nerve injury. Papers published in this journal emphasize morphological, physiological, and biochemical studies of injured neurons and glial cells, mechanisms and treatments of acute and chronic injury of the nervous system, neural and glial regeneration, transplantation, in vivo and in vitro injury models, cellular growth factors, blood flow, and metabolism of injured nervous tissues, and recovery of function. Both laboratory and clinical studies are encouraged. The journal will consider original research papers, short communications, reviews, and letters to the editor. Case reports are not accepted by the Journal. All submissions, except letters, must be accompanied by an abstract of about 250 words and keywords (<5). Original research papers should have an Introduction, Materials and Methods, Results, and Discussion sections. Short communications should have no sections and 6 manuscript pages or less, two tables or two figures or one of each. Reviews are invited and will be considered. PAGE CHARGES Page charges for this journal are set at $55.00 USD per typeset page. Nonpayment of page charges may result in a delay in publication. Costs for printing images in Anexos

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color are a separate fee and are not included in the page charge total. SUBMISSION OF MANUSCRIPTS Submissions to the journal will be reviewed by the editorial board. Every effort will be made to ensure a speedy review and a publication time of less than 6 months. Members of the editorial board will formulate a critique of the submitted manuscript. This critique will be sent to the author and, under special circumstances, may be published at the conclusion of the paper if the manuscript is accepted. A submitted manuscript (or any part of its essential substance) must not have been published or submitted for publication elsewhere before appearance in this journal (except abstracts in connection with scientific meetings). The journal is not responsible for lost manuscripts. Please read all the instructions to authors before submitting. MANUSCRIPTS GENERAL INSTRUCTIONS Full mailing information should be included if not on title page, then the following page. Corresponding author should be identified on title page. Prepare text doublespaced throughout. Leave ample margins on sides, top and bottom of the page. Please submit text in Microsoft Word. On the first page, give the full title of the paper, full name(s) and institutional affiliation(s) of author(s) with the highest academic degrees and institutional titles. Provide a running title (<45 characters) and a Table of Contents title (<75 characters), if the full title is longer than these limits. We require the full mailing address and contact information (telephone, fax, and e-mail address) for EACH author listed on your article. Please include the address (es). Please also indicate the corresponding author. Supply an abstract (<250 words) which presents the reasons for the study, the main findings (with specific data), the principal conclusions, and a list of key words (maximum of 5). Original research papers should contain the following sections: introduction, materials and Anexos

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methods, results, discussion, acknowledgments, references, tables, and figure legends. One subsection level is allowed. Short communications should be prepared similarly to original papers. Begin each section on a separate page. INSTANT ONLINE PUBLICATION The Journal publishes all accepted papers within 72 hours of acceptance in their unedited, uncorrected format. It is important to note that the information that is published online, and in all indexing services, is pulled directly from the data that is populated into the fields in Manuscript Central – NOT from the manuscript file – when the paper is originally uploaded to the system for peer review. Consequently, any errors contained in the system will remain on our website and all indexing services, including Medline, until the next revision of the article is published. As such, it is critical that authors enter all authors’ names correctly into the system at the time of submission. The next revision will take place after the corresponding author sees page proofs, makes any necessary corrections, and returns the changes to the Publisher. Once the alterations are completed, the revised version will be published on our website, and the newly corrected information will then be released to Medline/PubMed, in addition to any other indexing services in which the Journal is included. Please note that the typical time between acceptance of a paper and page proof distribution is approximately 4-8 weeks depending on the length and complexity of the paper. Journal of Neurotrauma is updating its referencing style to the numbered reference system. All submitted manuscripts should be prepared according to this

new

style.

Please

see

below

for

the

revised

instructions.

New Reference Style Anexos

99

Authors are responsible for the accuracy and completeness of their references. Number all references in the order they are cited in the text; do not alphabetize. Intext citations should be in numerical order, superscripted, not contained within parentheses or brackets, and placed after punctuation. All references in text should be included in the reference list, and all references in the reference list should have a corresponding citation in the main text of the manuscript. Preparation of Reference Section: Begin the Reference section on a separate page after the Author Disclosure Statement section Double-space entire section Personal communications, unpublished data, or manuscripts “in preparation” or “submitted for publication” should not be included in the Reference section. If necessary, these should be included at the appropriate place in the body of the text. Personal communications should include the contact’s first initial and last name, and the month and year of the communication. List all authors and/or editors for each listed article. Abbreviate

journal

titles

in

accordance

with

PubMed/Medline

(www.ncbi.nlm.nih.gov/pubmed/) For journal article titles, capitalize only the first letter of the title. References to abstracts should be indicated as such, with the abstract number included, if applicable For book citations, volume and edition numbers should be included when appropriate.

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Sample Styles: Lieutaud, T., Ndiaye, A., Laumon, B., and Chiron, M. (2012). Spinal cord injuries sustained in road crashes are not on the decrease in France: a study based on epidemiological trends. J. Neurotrauma 29, 479-487. Bele, S., and Brawanski, A. (2009). Biomarkers and surrogate markers, in: Neurotrauma and Critical Care of the Brain. J. Jallo, and C.M. Loftus (eds). Theime Publishing: New York, pps. 42-52. TABLE AND ILLUSTRATIONS Type tables double-spaced in a separate file, number tables with Arabic numerals, and provide a legend for each table. Tabular data should not be duplicated in figures. The top of the illustration should be indicated. A legend should be supplied for each illustration, and all legends numbered consecutively and provided (double-spaced) in a separate file. Figures should be numbered in the order cited in the text. A complete set should be submitted the manuscript. Images should not show the name of the manufacturer. Please keep in mind that the figures will be reduced, so please do not submit large figures/graphs that contain small type, as the text within the figure will not be readable after reduction. Photomicrographs should be cropped to 8cm width. Electron photomicrographs should have internal scale markers. If a figure consists of two or more parts, individual parts should have similar dimensions. Please follow these instructions carefully when preparing figure files for uploading: 1.

Do not include any illustrations as part of your text file.

2.

Do not prepare any figures in Word as they are not workable and will be rejected for production.

3.

Line illustrations must be submitted at 900 DPI.

4.

Halftones and color photos should be submitted at a minimum of 300 Anexos

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DPI. (NB: 600 DPI images are more desirable for production). 5.

PowerPoint files cannot be uploaded to Manuscript Central.

6.

Save art as either TIFF or EPS files. Do not submit JPEG files. (JPEG files are for screen representation-quality only and will print very poorly during the printing process.) To ensure proper print quality, please submit only TIFF or EPS files.

7.

Color art must be saved as CYMK not RGB. (NB: If RGB files are submitted, the files will be converted to CYMK and some color variation will occur).

8.

Label figures and tables inside the files in addition to naming the file with the figure or table number. (I.e., When figures or table files are opened, the figure or table number should appear inside the file.)

9.

When naming your figure files, please label them with your last name, followed by a period (.), and then list the figure number. Ex: Smith.Fig 1. Label figures and tables inside the files in addition to naming the file with the figure or table number. (I.e., when figure or table files are opened, the figure or table number should appear inside the file.)

Color illustrations can be printed in the journal with a subsidy from the author(s). Please contact the Publisher for further details. IMPORTANT: Please upload individual files of all manuscript material—do NOT upload a single PDF file containing all text, figure, and table files of your paper. Once all individual files are uploaded on to Manuscript Central, the system will automatically create a single PDF proof for you and the peer-review process. Disclosure Statement

Immediately following the Acknowledgments section, Anexos

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include a section entitled “Author Disclosure Statement.” In this portion of the paper, authors must disclose any commercial associations that might create a conflict of interest in connection with submitted manuscripts. This statement should include appropriate information for EACH author, thereby representing that competing financial interests of all authors have been appropriately disclosed according to the policy of the Journal. It is important that all conflicts of interest, whether they are actual or potential, be disclosed. This information will remain confidential while the paper is being reviewed and will not influence the editorial decision. Please see the Uniform Requirements for Manuscripts Submitted to Biomedical Journals at http://www.icmje.org/index.htlm#conflicts for further guidance. If no conflicts exist, the authors must state “No competing financial interests exist." If no conflicts exist, the authors must state “No competing financial interests exist." ABBREVIATIONS, NOMENCLATURE, AND SYMBOLS Consult the “Style Manual for Biologic Journals,” 4th Edition, 1978 (American Institute of Biological Sciences, 1401 Wilson Blvd, Arlington, VA 22209.) Identify medications, materials, and devices by full nonproprietary name, brand name, and the manufacturer’s name, city, state, and country. Place this information in parentheses in the text. PERMISSIONS Materials taken from other sources must be accompanied by a written statement from both author and publisher giving permission to the journal for reproduction. If clearances are required by the author’s institution, statements concerning such clearance should be provided in the manuscript.

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ANIMAL OR HUMAN EXPERIMENTATION Reports of research involving human and/or animal experimental subjects should be accompanied by a statement to the Editor, indicating approval by an Institutional Animal Care and Use Committee, Institutional Review Board or equivalent. PAGE PROOFS Page proofs are sent to the corresponding author via e-mail, so please be sure to have any e-mail filters accept e-mail from the liebertpub.com domain. Please ensure that proper e-mail addresses are given. REPRINTS Reprints may be ordered by following the special instructions that will accompany page proofs, and should be ordered at the time the corresponding author returns the corrected page proofs to the Publisher. Reprints ordered after an issue is printed will be charged at a substantially higher rate. DISCLAIMER The statements and opinions expressed in JOURNAL OF NEUROTRAUMA are those of the individual contributors, editors, or advertisers; they do not necessarily represent the views of the other editors or the publisher. Unless specified otherwise, the authors and publisher disclaim any responsibility or liability for such material. PUBLISHER The Journal is published by Mary Ann Liebert, Inc., publishers, 140 Huguenot Street, Floor, New Rochelle, NY 10801-5215. Telephone (914) 740-2100, Fax (914) 7402101, e-mail: [email protected]

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ANEXO 4 NORMAS DE PUBLICAÇÃO - Journal of Computer Assisted Tomography – Article 2

Online Submission and Review System

SCOPE The Journal of Computer Assisted Tomography is a peer-reviewed, multidisciplinary journal directed to an audience of radiology physicians. The journal publishes original articles in the form of original research, clinical investigations, review articles, case reports, technical notes, and clinical images. Ethical/Legal Considerations All manuscripts submitted to JCAT should comply with the guidelines of the February 2006 consensus statement of the International Committee of Medical Journal Editors, Uniform Requirements for Manuscripts Submitted to Biomedical Journals (Section II. Ethical Considerations in the Conduct and Reporting of Research). A copy of this document can be found at the ICMJE Web site (www.icmje.org). A submitted manuscript must be an original contribution not previously published (except as an abstract or preliminary report), must not be under consideration for publication elsewhere, and, if accepted, must not be published elsewhere in similar form, in any language, without the consent of Lippincott Williams & Wilkins. Each person listed as an author is expected to have participated in the study to a significant extent. Although the editors and referees make every effort to ensure the validity of published manuscripts, the final responsibility rests with the authors, not with the journal, its editors, or the publisher. All manuscripts must be submitted Anexos

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on-line through the journals Web site at http://jcat.edmgr.com/. See submission instructions on this page, under "On-line manuscript submission." Patient anonymity and informed consent: It is the author's responsibility to ensure that a patient's anonymity be carefully protected and to verify that any experimental investigation with human subjects reported in the manuscript was performed with informed consent and following all the guidelines for experimental investigation with human subjects required by the institution(s) with which all the authors are affiliated. Authors should remove patients' names and other identifying information from figures. If any identifying details appear in text, tables, and/or figures, the author must provide proof of informed consent obtained from the patient (i.e., a signed permissions form). Photographs with bars placed over eyes of patients should NOT be used in publication. If they are used, permission from the patient is required. Conflicts of interest Authors must state all possible conflicts of interest in the manuscript, including financial, consultant, institutional and other relationships that might lead to bias or a conflict of interest. If there is no conflict of interest, this should also be explicitly stated as none declared. All sources of funding should be acknowledged in the manuscript. All relevant conflicts of interest and sources of funding should be included on the title page of the manuscript with the heading “Conflicts of Interest and Source of Funding:”. For example: Conflicts of Interest and Source of Funding: A has received honoraria from Company Z. B is currently receiving a grant (#12345) from Organization Y, and is on the speaker’s bureau for Organization X – the CME organizers for Company A. For the remaining authors none were declared. Copyright: In addition, each author must complete and submit the journal’s copyright Anexos

106

transfer agreement, which includes a section on the disclosure of potential conflicts of interest based on the recommendations of the International Committee of Medical Journal Editors, “Uniform Requirements for Manuscripts Submitted to Biomedical Journals” (www.icmje.org/update.html). A

copy

of

the

form

can

be

obtained

by

clicking

on

the

following

link: http://edmgr.ovid.com/jcat/accounts/copyrightTransfer.pdf Completed forms must then be uploaded with the manuscript at the time of submission. Manuscripts can not be sent out for peer review until forms are submitted from each author. Please note that authors may sign the copyright transfer agreement form electronically. For additional information about electronically signing this form, go to http://links.lww.com/ZUAT/A106. Open access LWW’s hybrid open access option is offered to authors whose articles have been accepted for publication. With this choice, articles are made freely available online immediately upon publication. Authors may take advantage of the open access option at the point of acceptance to ensure that this choice has no influence on the peer review and acceptance process. These articles are subject to the journal’s standard peer-review process and will be accepted or rejected based on their own merit. Authors of accepted peer-reviewed articles have the choice to pay a fee to allow perpetual unrestricted online access to their published article to readers globally, immediately upon publication. The article processing charge for Journal of Computer Assisted Tomography is $2,000. The article processing charge for authors funded by Anexos

107

the Research Councils UK (RCUK) is $2,580. The publication fee is charged on acceptance of the article and should be paid within 30 days by credit card by the author, funding agency or institution. Payment must be received in full for the article to be published open access. Any additional standard publication charges, such as for color images, will also apply. Authors retain copyright Authors retain their copyright for all articles they opt to publish open access. Authors grant LWW a license to publish the article and identify itself as the original publisher. Creative Commons license Articles opting for open access will be freely available to read, download and share from the time of publication. Articles are published under the terms of the Creative Commons License Attribution-NonCommerical No Derivative 3.0 which allows readers to disseminate and reuse the article, as well as share and reuse of the scientific material. It does not permit commercial exploitation or the creation of derivative works without specific permission. To view a copy of this license visit: http://creativecommons.org/licenses/by-nc-nd/3.0. Compliance with NIH, RCUK, Wellcome Trust and other research funding agency accessibility requirements A number of research funding agencies now require or request authors to submit the post-print (the article after peer review and acceptance but not the final published article) to a repository that is accessible online by all without charge. As a service to our authors, LWW identifies to the National Library of Medicine (NLM) articles that require deposit and transmits the post-print of an article based on research funded in whole or in part by the National Institutes of Health, Howard Hughes Medical Institute, or other funding agencies to PubMed Central. The revised Copyright Transfer Agreement provides the mechanism. LWW ensures that authors can fully comply with the public access requirements of major Anexos

108

funding bodies worldwide. Additionally, all authors who choose the open access option will have their final published article deposited into PubMed Central. RCUK and Wellcome funded authors can choose to publish their paper as open access with the payment of an article process charge (gold route), or opt for their accepted manuscript to be deposited (green route) into PMC with an embargo. With both the gold and green open access options, the author will continue to sign the Copyright Transfer Agreement (CTA) as it provides the mechanism for LWW to ensure that the author is fully compliant with the requirements. After signature of the CTA, the author will then sign a License to Publish where they will then own the copyright. Those authors who wish to publish their article via the gold route will be able to publish under the terms of the Attribution 3.0 (CCBY) License. To view of a copy of this license visit: http://creativecommons.org/licenses/by/2.0/. Those authors who wish to publish their article via the green route will be able to publish under the rights of the Attribution

Non-commercial

3.0

(CCBY

NC)

license

(http://creativecommons.org/licenses/by-nc/2.0/). It is the responsibility of the author to inform the Editorial Office and/or LWW that they have RCUK funding. LWW will not be held responsible for retroactive deposits to PMC if the author has not completed the proper forms.

FAQ for open access http://links.lww.com/LWW-ES/A48 Permissions: Authors must submit written permission from the copyright owner (usually the publisher) to use direct quotations, tables, or illustrations that have appeared in copyrighted form elsewhere, along with complete details about the source. Any permissions fees that might be required by the copyright owner are the responsibility of the authors requesting use of the borrowed material, not the Anexos

109

responsibility of Lippincott Williams & Wilkins. Manuscript Submission On-line manuscript submission: All manuscripts must be submitted on-line through the new Web site at http://jcat.edmgr.com/. First-time users: Please click the Register button from the menu above and enter the requested information. On successful registration, you will be sent an e-mail indicating your user name and password. Print a copy of this information for future reference. Note: If you have received an e-mail from us with an assigned user ID and password, or if you are a repeat user, do not register again. Just log in. Once you have an assigned ID and password, you do not have to re-register, even if your status changes (that is, author, reviewer, or editor). Authors: Please click the log-in button from the menu at the top of the page and log in to the system as an Author. Submit your manuscript according to the author instructions. You will be able to track the progress of your manuscript through the system. If you experience any problems, please

contact

Jonathan

Scovner,

Managing

Editor,

at

[email protected], 215-521-8349 (telephone), or 215-827-5586 (fax). Requests for help and other questions will be addressed in the order received. Preparation of Manuscript Manuscripts that do not adhere to the following instructions will be returned to the corresponding author for technical revision before undergoing peer review. Form of manuscript: The submitted manuscript should conform to one of four styles: (a) Original Articles, presenting the results of original research or clinical investigations; (b) Review Articles, containing no new data but assessing a pertinent topic in the recent radiologic literature; (c) Case Reports, presenting imaging findings in four or fewer patients; and (d) Technical Notes, describing developments in Anexos

110

instrumentation or image processing. Title page: Include on the title page (a) complete manuscript title; (b) authors' full names, highest academic degrees, and affiliations; (c) name and address for correspondence, including fax number, telephone number, and e-mail address; (d) address for reprints if different from that of corresponding author; and (e) sources of support or individuals requiring acknowledgment. The title page must also include disclosure of funding received for this work from any of the following organizations: National Institutes of Health (NIH); Wellcome Trust; Howard Hughes Medical Institute (HHMI); and other(s). Structured abstract and key words: Limit the abstract for Original Articles to 150 words. Do not cite references in the abstract. Limit the use of abbreviations and acronyms. Use the following subheads: Objective, Methods, Results, and Conclusions. List three to five key words. OR Unstructured abstract and key words: Limit the abstract for Review Articles, Case Reports, and Technical Notes to 75 words. It must be factual and comprehensive. Limit the use of abbreviations and acronyms, and avoid general statements (e.g., "the significance of the results is discussed"). List three to five key words or phrases. Text: Organize the manuscript into four main headings: Introduction, Materials and Methods, Results, Discussion. Define abbreviations at first mention in text and in each table and figure. If a brand name is cited, supply manufacturer's name and address (city and state/country). Abbreviations: For a list of standard abbreviations, consult the Council of Biology Editors Style Guide (available from the Council of Science Editors, 9650 Rockville Pike, Bethesda, MD 20814) or other standard sources. Write out the full term for Anexos

111

each abbreviation at its first use unless it is a standard unit of measure. References: The authors are responsible for the accuracy of the references. Key the references at the end of the manuscript. Cite the references in text in the order of appearance. Cite unpublished data—such as papers submitted but not yet accepted for publication or personal communications—in parentheses in the text. If there are more than three authors, name only the first three authors and then use et al. Refer to the List of Journals Indexed in Index Medicus for abbreviations of journal names or access the list at http://www.nlm.nih.gov/tsd/serials/lji.html. Sample references are given below: Journal article 1. Farkas LG, Tompson B, Phillips JH, et al. Comparison of anthropometric and cephalometric measurements of the adult face. J Craniofacial Surg. 1999;10:18–25. Book chapter 2. Todd VR. Visual information analysis: frame of reference for visual perception. In: Kramer P, Hinojosa J, eds. Frames of Reference for Pediatric Occupational Therapy. Philadelphia: Lippincott Williams & Wilkins, 1999:205–256. Entire book 3. Kellman RM, Marentette LJ. Atlas of Craniomaxillofacial Fixation. Philadelphia, PA: Lippincott Williams & Wilkins; 1999. Software 4. Epi Info [computer program]. Version 6. Atlanta: Centers for Disease Control and Prevention; 1994. Online journals

5. Friedman SA. Preeclampsia: a review of the role of

prostaglandins. Obstet Gynecol [serial online]. January 1988;71:22–37. Available from: BRS Information Technologies, McLean, VA. Accessed December 15, 1990.

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112

Database 6. CANCERNET-PDQ [database online]. Bethesda, MD: National Cancer Institute; 1996. Updated March 29, 1996. World Wide Web 7. Gostin LO. Drug use and HIV/AIDS [JAMA HIV/AIDS Web site]. June 1, 1996. Available at: http://www.ama-assn.org/special/hiv/ethics. Accessed June 26, 1997. Figures: A) Creating Digital Artwork 10.

Learn

about

the

publication

requirements

for

Digital

Artwork:

http://links.lww.com/ES/A42 11.

Create, Scan and Save your artwork and compare your final figure to

the Digital Artwork Guideline Checklist (below). 12.

Upload each figure to Editorial Manager in conjunction with your

manuscript text and tables. 13. B) Digital Artwork Guideline Checklist Here are the basics to have in place before submitting your digital artwork: •

Artwork should be saved as TIFF, EPS, or MS Office (DOC, PPT, XLS)

files. High resolution PDF files are also acceptable. •

Crop out any white or black space surrounding the image.



Diagrams, drawings, graphs, and other line art must be vector or saved

at a resolution of at least 1200 dpi. If created in an MS Office program, send the native (DOC, PPT, XLS) file. •

Photographs, radiographs and other halftone images must be saved at

a resolution of at least 300 dpi. •

Photographs and radiographs with text must be saved as postscript or Anexos

113

at a resolution of at least 600 dpi. •

Each figure must be saved and submitted as a separate file. Figures

should not be embedded in the manuscript text file. Remember: •

Cite figures consecutively in your manuscript.



Number figures in the figure legend in the order in which they are

discussed. •

Upload figures consecutively to the Editorial Manager web site and

enter figure numbers consecutively in the Description field when uploading the files. Figure legends: Include legends for all figures. They should be brief and specific, and they should appear on a separate manuscript page after the references. Use scale markers in the image for electron micrographs, and indicate the type of stain used. Color figures: The journal accepts for publication color figures that will enhance an article. Authors who submit color figures will receive an estimate of the cost for color reproduction. If they decide not to pay for color reproduction, they can request that the figures be converted to black and white at no charge. Tables: Create tables using the table creating and editing feature of your word processing software (e.g., Word, WordPerfect). Do not use Excel or comparable spreadsheet programs. Group all tables in a separate file. Cite tables consecutively in the text, and number them in that order. Key each on a separate page, and include the table title, appropriate column heads, and explanatory legends (including definitions of any abbreviations used). Do not embed tables within the body of the Anexos

114

manuscript. They should be self-explanatory and should supplement, rather than duplicate, the material in the text. Style: Pattern manuscript style after the American Medical Association Manual of Style (9th edition). Stedman's Medical Dictionary (27th edition) and Merriam Webster's Collegiate Dictionary (10th edition) should be used as standard references. Refer to drugs and therapeutic agents by their accepted generic or chemical names, and do not abbreviate them. Use code numbers only when a generic name is not yet available. In that case, supply the chemical name and a figure giving the chemical structure of the drug. Capitalize the trade names of drugs and place them in parentheses after the generic names. Supplemental Digital Content: Authors may submit supplemental digital content via Editorial Manager to enhance their article's text and to be considered for online-only posting. Supplemental digital content may include the following types of content: text documents, graphs, tables, figures, graphics, illustrations, audio, and video. Cite all supplemental digital content consecutively in the text. Citations should include the type of material submitted, should be clearly labeled as "Supplemental Digital Content," should include a sequential number, and should provide a brief description of the supplemental content. Provide a legend of supplemental digital content at the end of the text. List each legend in the order in which the material is cited in the text. The legends must be numbered to match the citations from the text. Include a title and a brief summary of the content. For audio and video files, also include the author name, videographer, participants, length (minutes), and size (MB). No patientidentifying information should be used in supplemental digital content unless written consent from the patient, the patient’s parents or the patient’s guardian has been obtained. Documentation regarding this consent must be submitted with the Anexos

115

manuscript.

Copyright

and

Permission

forms

for

article

content

including

supplemental digital content must be provided at the time of submission. Supplemental Digital Content Size & File Type Requirements: To ensure a quality experience for those viewing supplemental digital content, it is suggested that authors submit supplemental digital files no larger than 10 MB each. Documents, graphs, and tables may be presented in any format. Figures, graphics, and illustrations should be submitted with the following file extensions: .tif, .eps, .ppt, .jpg, .pdf, .gif. Audio files should be submitted with the following file extensions: .mp3, .wma. Video files should be submitted with the following file extensions: .wmv, .mov, .qt, .mpg, .mpeg, .mp4. Video files should also be formatted with a 320 X 240 pixel minimum screen size. For more information, please review LWW's requirements for submitting supplemental digital content: http://links.lww.com/A142. After Acceptance Page proofs and corrections: Corresponding authors will receive electronic page proofs to check the copyedited and typeset article before publication. Portable document format (PDF) files of the typeset pages and support documents (e.g., reprint order form) will be sent to the corresponding author by email. Complete instructions will be provided with the e-mail for downloading and printing the files and for faxing the corrected page proofs to the publisher. Those authors without an e-mail address will receive traditional page proofs. It is the author's responsibility to ensure that there are no errors in the proofs. Changes that have been made to conform to journal style will stand if they do not alter the authors' meaning. Only the most critical changes to the accuracy of the content will be made. Changes that are stylistic or are a reworking of previously accepted material will be disallowed. The publisher reserves the right to deny any changes that do not affect the accuracy of the content. Authors may be charged for alterations to the proofs Anexos

116

beyond those required to correct errors or to answer queries. Proofs must be checked carefully and corrections faxed within 24 to 48 hours of receipt, as requested in the cover letter accompanying the page proofs. Reprints: Authors will receive a reprint order form and a price list with the page proofs. Reprint requests should be faxed to the publisher with the corrected proofs, if possible. Reprints are normally shipped 6 to 8 weeks after publication of the issue in which the item appears. Contact the Reprint Department with any questions: Lippincott Williams & Wilkins, 351 W. Camden St., Baltimore, MD 21201. Fax: (410) 528-4434. Publisher's contact: Fax corrected page proofs, reprint order form, and any other related materials to Journal Production Editor, Journal of Computer Assisted Tomography, (717) 633-8928 or (717) 633-8943.

Anexos

117

ANEXO 5

TEMPO DE REALIZAÇÃO DA TC CONTROLE – TRAUMA

Anexo 5 – Porcentagem de pacientes x tempo em que foi realizada a tomografia computadorizada de controle nos casos de contusão cerebral traumática, no grupo com a presença do spot sign e no grupo sem a presença deste achado.

Realização

Grupo de

Grupo de pacientes

da TC

pacientes com

sem a presença do

controle

Spot Sign

Spot Sign

24 h

58%

60%

48 h

20%

30%

> 48 h

22%

10%

Anexos

Loading...

marcos rosa júnior - Faculdade de Ciências Médicas da Santa Casa

MARCOS ROSA JÚNIOR SPOT SIGN COMO FATOR PREDITOR DE CRESCIMENTO E IMPLICAÇÕES PROGNÓSTICAS NAS HEMORRAGIAS INTRAPARENQUIMATOSAS CEREBRAIS NÃO RELACIO...

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