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
14
4. RESULTADOS
15
Seção: Articles – Article 1
Resultados
16
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
19
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
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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
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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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24
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
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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
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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.
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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.
Resultados
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).
Resultados
32
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
Resultados
33
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.
Resultados
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
Resultados
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.
Resultados
39
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).
Resultados
45
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.
Resultados
46
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.
Resultados
47
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Resultados
53
Seção: Articles – Article 2
Journal of Computer Assisted Tomography Decision
Resultados
54
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
55
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.
Resultados
56
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
57
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
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58
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).
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59
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.
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60
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
Resultados
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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
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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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63
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
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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
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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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66
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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67
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
69
*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.
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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.
Resultados
75
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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.
Resultados
78
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.
Resultados
79
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
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7. ANEXOS
92
ANEXO 1
APROVAÇÃO COMITÊ DE ÉTICA
Anexos
93
Anexos
94
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
95
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
96
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
97
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
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(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
98
methods, results, discussion, acknowledgments, references, tables, and figure
legends. One subsection level is allowed. Short communications should be prepared
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INSTANT ONLINE PUBLICATION
The Journal publishes all accepted papers within 72 hours of acceptance in their
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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
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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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100
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
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101
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,
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102
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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103
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
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105
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
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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
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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
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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
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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
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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
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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
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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
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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
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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
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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.
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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%
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