1 ¿Por qué es importante clasificar los ictus? ¿Cómo los podemos

Ictus isquémico
PROGRAMA DE FORMACIÓ CONTINUADA EN RADIODIAGNÒSTIC
CURS BASIC
Curs 2012‐2013
Clasificación radiológica de los infartos cerebrales.
g
Topografía y etiología.
¾87% de todos los ictus
¾Incrementa el riesgo:
9Recurrencias
9Enfermedad coronaria
9Enfermedad vascular periférica
Àlex Rovira Cañellas
Unitat RM. Servei de Radiologia
Hospital Vall d’Hebron
Barcelona. ¾Medidas de prevención secundaria necesarias
[email protected]‐cat.org
¿Por qué es importante clasificar los ictus?
¾Seleccionar estrategia terapéutica en fase aguda
¾Establecer terapias de prevención secundaria
¾Riesgo de recurrencias, pronóstico
¾Indicación pruebas diagnósticas
¾Selección para ensayos clínicos
¾Comparación de cohortes
Clasificación precisa y precoz
¿Cómo los podemos clasificar?
¾Perfiles de riesgo
¾Hallazgos clínicos
¾Marcadores biológicos, genéticos
¾P b di ó ti
¾Pruebas diagnósticas
9EKG
9Doppler
9Ecocardiografía
9TC: simple y avanzada
9RM: convencional y avanzada
9Angiografía por sustracción digital
1
Oxfordshire Community
Oxfordshire Community Stroke Project (topografía y extensión)
•Basado en signos y síntomas clínicos
•Predice pronóstico
•Buena correlación con los hallazgos radiológicos (TC)
TOAST (Trial of rial of O
ORG 10172 in RG 10172 in A
Acute Stroke Treatment
reatment))
Guias desarrolladas por clasificar prospectivamente los infartos en función de su mecanismo de origen
9Perfiles de riesgo: edad, diabetes, colesterol, HTA
9Hallazgos clínicos
9Pruebas paraclínicas: cerebrales, vasos, corazón
1. Total anterior circulation infarcts (TACI) 15‐17%
f
(
)
1 Enf. de gran vaso (15‐20%)
1.
Enf de gran vaso (15 20%)
2. Partial anterior circulation infarcts (PACI) 35%
2. Enf. de pequeño vaso (25%)
3. Lacunar infarcts (LACI) 25%
3. Cardioembolismo (15‐27%)
4. Posterior circulation infarcts (POCI) 25%
4. Otras etiologías (2%) (vasculitis, disección arterial,…)
5. Indeterminados o etiologías múltiples (~35%)
•No predice mecanismo de infarto
•Fácil de implementar en urgencias
9Precisión depende de la extensión y calidad de pruebas paraclínicas realizadas
Bamford et al. Lancet 1991
Clasificación infartos basado en estudios NRx
Clasificación infartos basado en estudios NRx
Topografía
Adams et al. Stroke 1993
Infartos territoriales anteriores
Masivos
Parciales
1. Infartos territoriales circulación anterior
2. Infartos territoriales circulación posterior ¾Infartos masivos
3. Infartos lacunares
Afectan al menos 2 de los 3 territorios silvianos
Elevada frecuencia de progresión clínica
Elevada mortalidad
4. Infartos centro oval
5. Infartos frontera
Mecanismo causal: TC/RM + estudio vascular
Lee et al. Stroke 2000
2
Infartos territoriales anteriores
¾Infartos masivos: mecanismo causal
¾Infartos masivos: Infarto MALIGNO
9Cardioembolismo
9Oclusión ACI
9Disección ACI
Infarto completo o casi completo de la ACM
10% de todos los infartos
Deterioro clínico a los 2‐5 días
80% mortalidad
C i t í d
Craniotomía decompresiva reduce mortalidad
i
d
t lid d
Vahedi et al. Lancet Neurol 2007 Cardioembolismo
Oclusión ACI – Enf. gran vaso
Hemicraniectomía en infartos malignos ACM
Seguimiento UCI
Hemicraniectomia si:
Desviación > 5 mm y/o PIC > 20 mmHg
Desviación ≥ 5mm
Hemicraniectomia
Pooled analysis of DECIMAL, DESTINY, HAMLET clinical trials
Tras cirugía descompresiva la probabilidad de supervivencia aumenta del 28% a casi el 80% y la probabilidad de alcanzar un mRS ≤3 se dobla.
basal
24 h
48 h
48 h
6 d
Vahedi et al. Lancet Neurol 2007
3
¾Infartos masivos
Infartos territoriales anteriores
¾Infartos parciales
¾Infartos parciales
Afectan sólo 1 de los 3 territorios silvianos
Baja frecuencia de progresión clínica
Baja mortalidad
Origen:
g
9Cardioembolismo y ateroesclerosis de gran vaso
Infartos arteria cerebral anterior
Infartos arteria cerebral anterior
¾Baja incidencia: ~1% de ictus isquémicos
9% bilaterales
4% completos
9A
9Ateroesclerosis
l
i gran vaso: 73%
Enfermedad ACA
Enfermedad ACI
Ambas
9Cardioembolismo: 10%
9Indeterminado: 15%
Embolismo A-A
Oclusión proximal
Oclusión rama
Kang et al. Neurology 2008
Kang et al. Neurology 2008
4
Infartos agudos múltiples multiterritoriales (AMBI)
Infartos arteria cerebral anterior
Circ. anterior / un hemisferio 44%
Cardioembolismo
oesclerótica gran vaso
Enf. atero
¾Alta incidencia de disecciones (43%): causa más frecuente de
infarto aislado de la ACAnt (jóvenes) (Sato et al. Cerebrovasc Dis 2009)
Circ. anterior / ambos hemisfer. 21%
Embolismo A‐A
Circ. Posterior
23%
4.
Cardioembolismo
Enf. pequeño vaso
Aumento fibrinógeno o hematocrito; microangiopatía trombótica
Variantes anatómicas circ. anterior
Cardioembolismo
Cardíaco
Arco aórtico
Embolismo
Circ. Anterior y posterior
12%
1.
2.
3.
1.
2.
Ateroesclerosis gran vaso
A Com Post persistente; ACP fetal
Jae‐Kyu Roh et al. Stroke 2000
Infartos circulación posterior
Infartos territoriales posteriores
Distal
Medio
Proximal
PICA
AICA
ACS
ACP
Caplan LR. et al. Ann Neurol 2004
5
Infartos circulación posterior
Infartos circulación posterior: proximal
Distal
Embolismo
40
35
Proximal
Hemodinámico
30
25
Medio
20
Oclusión rama
15
10
5
0
> 2/3 Ateroesclerosis de gran vaso (sistema vertebro basilar intra y extracraneal)
Hemodinámico Embolismo arterio‐arterial
cardíaco
arterial
Caplan LR. et al. Ann Neurol 2004
Caplan LR. et al. Ann Neurol 2004
Infartos territoriales de circulación posterior
Mecanismos ictus (Caplan, 1996; Glass 2002)
Mecanismos causales (Caplan, 1996; Glass 2002)
¾Enfermedad oclusiva de gran vaso – oclusion ramas: disección arteria vertebral
¾Enf. oclusiva de ramas arteriales
Arterias circunferenciales
29% de infartos latero‐bulbares secundarios a disección de la AV
Kameda et al. Stroke 2004
Arterias perforantes
cortas
largas
6
Infartos paramedianos pontinos
Enf de gran vaso
Lesión rama con origen en a. basilar
Enf. de pequeño vaso
Cardioembolismo
El sistema arterial perforante
El sistema arterial perforante
Oclusión proximal de una arteria perforante
A. Coroidea anterior (AChoA)
A. lenticuloestriadas (ACM)
A. lenticuloestriadas (ACA)
A. de Heubner (ACA)
A. talamoperforantes (ACP)
Enf. pequeño vaso
Erro et al. Eur J Neurol 2005
Erro et al. Eur J Neurol 2005
Cortesía Dr. Hendriksen. 7T
Infartos lacunares
Infartos lacunares
El sistema arterial perforante
El sistema arterial perforante
A. Coroidea anterior (AChoA)
A. lenticuloestriadas (ACM)
•Infartos pequeños (<1.5cm) por oclusión/lesión de una arteria perforante única con origen en el polígono de Willis o de la arteria basilar
•Corresponden al 11‐25% de ictus isquémicos
•La mayoría son asintomáticos
•Solitarios o múltiples
•Mecanismo causal variable: enf. de pequeño vaso (75%)
A. lenticuloestriadas (ACA)
A. talamoperforantes (ACP)
A. de Heubner (ACA)
9Ateroesclerosis
9C di
9Cardioembolismo
b li
9Disección arterial
9Trombosis local (estados hipercoag.)
Micheli et al. J Neurol 2008
7
Infartos lacunares
Infartos lacunares grandes (únicos)
Infartos lacunares
Infartos lacunares pequeños (múltiples)
Arteriopatía no ateroesclerótica
•Microateromatosis
•Oclusión proximal de una arteria perforante grande
•Frecuentemente sintomáticos
•No asociados siempre a hipertensión arterial
•Sin lesiones isquémicas/hemorrágicas crónica asociadas (TC/RM)
•Lesión destructiva de arterias penetrantes pequeñas (<200μm).
Lipohialinosis
•Frecuentemente asintomáticos
•Asociados a hipertensión arterial crónica, DM, hematocritos altos
•Con lesiones isquémicas/hemorrágicas crónica asociadas
•Elevada
El d tasa
t
d recurrencias
de
i (24.3%
(24 3% vs 7.7%),
7 7%) peor pronóstico
ó ti
Arauz et al. Stroke 2003
Jackson et al. Stroke 2010
Infartos subcorticales pequeños (<20mm) y únicos Infartos subcorticales pequeños y únicos Arterias perforantes
Arterias perforantes ACM
Arterias perforantes
Arterias perforantes ACM
Nah et al. Stroke 2010
Distal
Proximal sin lesión vascular
Distal sin lesión vascular
Proximal sin lesión vascular
Proximal con lesión vascular
Proximal con lesión vascular
Nah et al. Stroke 2010
8
Infartos subcorticales pequeños y únicos Infartos lacunares
Infartos lacunares
Arterias perforantes
Arterias perforantes ACM
Arterias perforantes ACM/basilar
Arterioesclerosis
Distal sin lesión vascular
Enf. de pequeño vaso
Proximal sin lesión vascular
No predileción
Proximal con lesión vascular
Arterioesclerosis
Enf. de pequeño vaso
Nah et al. Stroke 2010
Infartos lacunares
Infartos lacunares
Infartos frontera
Afectan la unión distal de dos territorios arteriales no‐anostomóticos presión de perfusión baja
¾10% de primeros ictus isquémicos ¾75% de ictus tardíos en oclusiones ACI
¾5% de ictus iniciales en oclusiones ACI 5% de ictus iniciales en oclusiones ACI
¾Mecanismo causal no completamente conocido
Aterosclerosis
Lipohialinosis
Perfusión miseria
Embolismo (arterio‐arterial)
Distal con lesión vascular
Mangla et al. Radiographics 2011
9
Topografía de los infartos frontera
Patogénesis de los infartos frontera
Dos procesos interrelacionados:
•hipoperfusión
•embolización
Infartos frontera internos
Infartos frontera corticales anteriores
Infartos frontera corticales posteriores
Momjian‐Mayor I, et al. Stroke 2005; Yong SW. et al. Stroke 2006
Infartos frontera externos (corticales)
¾Localización variable
9 Circulación colateral leptomençingea
9 Diferencias individuales
Infartos frontera internos (subcortical)
¾Mas frecuentes entre arterias lenticuloestriadas y ACM superficial
¾Paraventricular: patrón en rosario
¾Difícil de diferenciar de infartos territoriales
Mecanismos:
Mechanismos:
Embolismo
No asociado a compromiso hemodinámico
Compromiso hemodinámico (estenosis‐oclusión arterial)
Peor pronóstico
Deterioro clínico
Perfusión de miseria (PWI)
Microembolias (corazón o gran vaso)
Infarto frontera subcortical
Infartos corticales
Área de baja perfusión (limitada capacidad de lavado)
Momjian‐Mayor I, et al. Stroke 2005; Yong SW. et al. Stroke 2006
Momjian‐Mayor I, et al. Stroke 2005;Yong SW. Et al. Stroke 2006
10
Compromiso hemodinámico territorio frontera: perfusión miseria
Infarto frontera interno: perfusión miseria
FLAIR
TTP
ASL
DWI
Hipoperfusión en oclusiones ACI
Infartos frontera: compromiso hemodinámico
Infartos frontera: ateroesclerosis intracraneal, disección arterial
11
Conclusiones
•Los informes radiológicos deben utilizar una clasificación objetiva
de los ictus isquémicos
•La RM (utilizando secuencias convencionales, de difusión y
angiográficas)) permite una aproximación temprana al mecanismo
angiográficas
causal de los ictus isquémicos
•Esta información puede tener impacto en la toma de decisiones
terapéuticas
12
1
CLASIFICACIÓN TOPOGRÁFICA Y CAUSAL DE LOS ICTUS ISQUÉMICOS
Alex Rovira Cañellas,
Unidad Resonancia Magnética. Servicio de Radiología
Hospital Universitario Vall d’Hebron
Passeig Vall d’Hebron 119-129
08035 Barcelona
e-mail: [email protected]
Introducción
Clasificación neurorradiológica
ƒ
Infartos del sistema arterial pial o leptomeníngeo
ƒ
Infartos del sistema arterial perforante. Infartos lacunares
ƒ
Infartos del centro oval
ƒ
Infartos frontera
ƒ
Infartos agudos múltiples sincrónicos
INTRODUCCIÓN
El ictus isquémico se considera una emergencia médica ya que el pronóstico de los
pacientes que lo presentan depende de la rapidez con que se adopten las medidas
adecuadas para reducir el daño cerebral y disminuir el riesgo de recurrencias. El
objetivo principal, por lo que hace referencia a la actuación médica, es conseguir que
los pacientes con un ictus isquémico agudo (incluyendo los episodios transitorios)
puedan ser evaluados, diagnosticados y tratados adecuadamente y de manera urgente
en un centro hospitalario que disponga de una atención organizada del mismo. Para
lograr
este
objetivo,
tienen
una
especial
relevancia
las
exploraciones
neurorradiológicas, que no sólo permiten diferenciar un ictus isquémico de uno
hemorrágico y descartar lesiones causales del cuadro clínico de origen no vascular,
sino que ofrecen además información sobre la presencia, características y extensión del
tejido isquémico, así como de la lesión vascular causante del mismo. La primera parte
de este capítulo profundizará en la clasificación topográfica y causal de los infartos, y la
2
segunda, revisará el papel actual de las diferentes técnicas neuroradiológicas en la
valoración del ictus isquémico en fase aguda, especialmente en el contexto de un
potencial tratamiento recanalizador.
CLASIFICACIÓN TOPOGRÁFICA Y CAUSAL DE LOS ICTUS ISQUÉMICOS
Establecer un diagnóstico precoz y preciso tanto topográfico como etiológico de los
diferentes tipos de ictus isquémico tiene influencia sobre su manejo clínico, pronóstico,
riesgo de recurrencia y tratamiento específico.
Los ictus isquémicos se pueden clasificar en relación con sus características
topográficas y mecanismo causal en base a diferentes datos entre los que se incluyen
el perfil de riesgo de los pacientes, los hallazgos clínicos, diferentes marcadores
biológicos o genéticos y finalmente y, de forma especialmente relevante, las
alteraciones detectables en diferentes pruebas diagnósticas que se pueden dividir en
tres grandes grupos: cardiológicas (electrocardiograma, ecocardiografía), vasculares
(Doppler transcraneal y cervical, angio-TC, angio-RM, angiografía intraarterial) y
parenquimatosas cerebrales (TC, RM).
Clasificación neurorradiológica
La
gran
evolución
que
ha
experimentado
el
diagnóstico
neurorradiológico,
especialmente con la utilización de la RM y de técnicas avanzadas de TC, que
combinan el análisis del parénquima cerebral y de los vasos cráneo-cervicales, ha
permitido realizar un diagnóstico más preciso y rápido de la topografía y mecanismo
causal de los ictus isquémicos. Desde el punto de vista topográfico, los infartos se
pueden clasificar en los siguientes grupos:
• Infartos territoriales de la circulación anterior
• Infartos territoriales de la circulación posterior
• Infartos lacunares
• Infartos del centro oval
• Infartos frontera
• Infartos agudos múltiples sincrónicos
3
Infartos del sistema arterial pial o leptomeníngeo
1. Infartos territoriales de la circulación anterior
El territorio anterior corresponde a aquellas áreas del cerebro irrigadas por las
arterias carótidas internas y sus ramas. Son el tipo más común de ictus isquémicos,
representando aproximadamente el 70% del total de los mismos.
La oclusión de la arteria cerebral media (ACM) o de sus ramas es la causa más
frecuente de infartos de la circulación anterior (>90%), los cuales de dividen según
su extensión en masivos o parciales.
Los infartos masivos de la circulación anterior son aquellos que afectan al menos a
dos de los tres principales territorios silvianos (superficial anterior, superficial
posterior y profundo). Estos infartos muestran una elevada frecuencia de progresión
clínica y mortalidad. El mecanismo causal de estos infartos suele ser
cardioembólico, o por oclusión aterotrombótica o disección de la arteria carótida
interna.
Existe un subtipo de infarto masivo de la ACM, denominado infarto maligno, que se
produce cuando se afecta de forma completa o casi completa al territorio silviano,
con una rápida progresión en el efecto de masa por desarrollo de edema masivo.
Representa un 10% de todos los infartos, y se asocia a una mortalidad de
aproximadamente el 80% tras un deterioro clínico que se produce generalmente
entre el 2º-5º día tras el episodio clínico inicial. En estos pacientes la craniectomía
descompresiva realizada en las primeras 48 horas tras el inicio del ictus, es una
medida que reduce la mortalidad y mejora el pronóstico. La identificación de un
infarto masivo mediante TC o RM especialmente si va asociado a una oclusión de la
arteria carótida interna en pacientes jóvenes, predice un elevado riesgo de
desarrollar un infarto maligno de la ACM (perfil maligno).
Los infartos parciales de la circulación anterior afectan sólo a uno de los tres
territorios silvianos principales. Tanto la progresión clínica como la mortalidad son
más bajas en relación con los infartos masivos. El origen suele ser cardioembólico o
por aterosclerosis de gran vaso en porcentajes similares.
La diferencia en el tamaño de los infartos silvianos ayuda a orientar su mecanismo
causal. Así, cuanto más proximal sea la oclusión arterial que produce el infarto,
4
mayor será su tamaño, y a su vez, cuanto mayor sea el tamaño del trombo, más
proximal se situará la oclusión arterial. De esta forma, los trombos de origen
cardíaco, en ocasiones de gran de mayor tamaño, ocluirán con más frecuencia los
segmentos proximales y producirán con mayor frecuencia infartos masivos, mientras
que los de origen embólico arterio-arterial de causa aterotrombótica producen
infartos de menor tamaño que en ocasiones adoptan un patrón fragmentado uniterritorial.
Los infartos de la arteria cerebral anterior (ACA) representan aproximadamente un
1% del total de infartos. Hasta un 9% son bilaterales y solamente un 4% son
completos. La causa más frecuente es la aterosclerosis de gran vaso, afectando
bien la propia ACA, la arteria carótida interna o ambas. En pacientes con infartos
aislados de la ACA la disección arterial es un mecanismo causal frecuente pero que
con frecuencia se infradiagnostica. La etiología cardioembólica representa el 10%,
mientras que un 15% son de origen indeterminado.
2. Infartos territoriales de la circulación posterior
La RM es la técnica de imagen con mayor sensibilidad en la detección y
caracterización topográfica de los infartos de la fosa posterior.
Una clasificación de estos infartos, basada en la distribución territorial arterial, facilita
el determinar su mecanismo causal más probable:
1. Territorio proximal (arterias vertebrales y cerebelosas postero-inferiores):
más de dos tercios de estos infartos se producen como consecuencia de un
compromiso hemodinámico o a embolismos arterio-arteriales secundarios a
enfermedad aterotrombótica de gran vaso tanto de las arterias intra como
extracraneales. Hasta un 29% de los infartos proximales que afectan la
región lateral del bulbo son secundarios a disección de la arterial vertebral.
La extensión de estos infartos proximales se ha asociado con su
mecanismo de origen, siendo de mayor tamaño los secundarios a
enfermedad aterotrombótica en comparación con los secundarios a
disección de la arteria vertebral.
5
2. Territorio medio (tronco basilar y arterias cerebelosas antero-inferiores): se
producen generalmente por ateroesclerosis del tronco basilar, o por
microateromatosis del origen de las arterias perforantes o circunflejas
cortas (infartos grandes) o por enfermedad lipohialinótica de las arterias
perforantes (infartos pequeños).
3. Territorio distal (arterias cerebelosas superiores, top de la basilar y arterias
cerebrales posteriores): el mecanismo causal más frecuente es el
embolismo de origen cardíaco o arterio-arterial.
Infartos del sistema arterial perforante. Infartos lacunares
El sistema perforante lo componen las arterias que penetran en el parénquima
encefálico desde su emergencia en el polígono de Willis, en la arteria coroidea anterior
o en la arteria basilar (arterias perforantes). Estas arterias irrigan los ganglios de la
base, el tálamo, subtálamo y epitálamo, la cápsula interna y la región paramediana del
tronco. Estos infartos se producen por la oclusión (proximal o distal) de una arteria
perforante. Por definición el diámetro de los infartos lacunares no debe superar los 15
mm en la fase crónica, si bien en las fases precoces pueden ser mayores debido a la
presencia de edema.
Los infartos lacunares se producen con mayor frecuencia por oclusión de las arterias
lentículo-estriadas, las tálamo-perforantes y las perforantes con origen en la arteria
coroidea anterior. Representan entre el 11 y 25% de los ictus, si bien la mayoría
resultan asintomáticos. El mecanismo causal en el 75% de los casos es la enfermedad
de pequeño vaso (microateromatosis o lipohialinosis) y menos de un 25% son
secundarios a embolismos arteria-arteria, a cardioembolismo, a disección arterial o a
trombosis local por hipercoagulabilidad. Estas causas menos frecuentes confieren un
peor pronóstico.
Los infartos lacunares que afectan los hemisferios cerebrales se pueden dividir en dos
grandes grupos:
1. Infartos lacunares grandes: la causa más frecuente es la microateromatosis
que afecta el origen de una arteria perforante (habitualmente con origen en
6
las arterias coroidea anterior y cerebral media), que produce su oclusión y
consecuentemente infartos grandes, proximales y sintomáticos. Con
frecuencia estos infartos se presentan de forma aislada, es decir sin
asociarse a otras lesiones isquémicas cerebrales (desmielinización,
microsangrados, infartos crónicos) y no se suelen asociar a hipertensión
arterial. En este tipo de infartos la obtención de estudios de RM con
secuencias ponderadas en T1 de alta resolución demuestran con
frecuencia placas ateromatosas en el segmento horizontal de la ACM.
2. Infartos lacunares pequeños: se producen por una destrucción de las arterias
perforantes pequeñas (<200 micras) en el contexto de una enfermedad
lipohialinótica generalmente asociada a hipertensión arterial crónica. Estos
infartos
suelen
acompañarse
de
otras
lesiones
isquémicas
y
a
microsangrados. Son infartos de pequeño tamaño y de localización distal
que con frecuencia son asintomáticos, y que se localizan habitualmente en
la región estriato-capsular y talámica. Tienen una mayor tasa de
recurrencias y un peor pronóstico que los infartos lacunares aislados
secundarios a microateromatosis.
Los infartos lacunares del tronco afectan predominantemente la región paramediana de
la protuberancia, y se producen como consecuencia de una oclusión proximal o distal
de las arterias perforantes con origen en el tronco basilar. Estos infartos paramedianos
de tronco se pueden clasificar de forma similar a la descrita para los infartos lacunares
que afectan los hemisferios cerebrales:
1. Infartos paramedianos grandes: son infartos de gran tamaño que de forma
constante afectan el margen anterior de la protuberancia y que se producen
como consecuencia de una oclusión proximal de una arteria perforante
secundaria
a
una
ateromatosis
de
la
arteria
basilar
o
a
una
microateromatosis que afecta su origen. En este tipo de infartos es
frecuente la existencia de patología ateroesceróstica en la arteria fácilmente
demostrable en secuencias ponderadas en T1 de alta resolución
7
2. Infartos paramedianos parciales, son infartos de menor tamaño y en
situación distal, generalmente secundarios a enfermedad lipohialinótica de
pequeño vaso secundaria a hipertensión arterial crónica. Estos infartos
tiene una localización distal en la región paramediana de la protuberancia,
respetando por tanto su margen anterior.
Infartos del centro oval
El centro oval es la región de la sustancia blanca de los hemisferios cerebrales irrigada
por arterias medulares (origen en las arterias leptomeníngeas), que comprende la
mayoría de la corona radiata superficial y los fascículos de asociación intrahemisféricos.
Los infartos que afectan el centro oval incluyen los que se producen por oclusión de las
arterias propias de dicha región (arterias medulares), así como los que afectan áreas
limítrofes entre las arterias medulares y otros territorios arteriales (infartos frontera
internos).
Los infartos del centro oval pueden subdividirse en dos tipos en base a su tamaño:
1. Infartos mayores: son infartos grandes (>15 mm) que no se pueden explicar
por una oclusión de una única arteria medular Se suelen producir como
consecuencia de un compromiso hemodinámica secundario a una
estenosis grave carotídea o de la arteria cerebral media homolateral.
Corresponden a infartos frontera internos.
2. Infartos menores (<15 mm): afectan a una sola rama medular y suelen ser
secundarios a enfermedad lipohialinótica de pequeño vaso o por
embolismos arterio-arteriales o de origen cardíaco. En esta última situación
es frecuente que los estudios de difusión por RM muestren infartos
adicionales de distribución fragmentada que afectan la sustancia gris
cortical, en cuyo caso es más adecuado clasificarlos como infartos
territoriales fragmentados de la circulación anterior.
Infartos frontera
Los infartos frontera son aquellos que afectan a la unión distal de al menos dos
territorios arteriales. El mecanismo causal de este tipo de infartos no está del todo bien
8
establecido, si bien parecen ser consecuencia de un compromiso hemodinámico
(infartos de bajo flujo) secundario a una estenosis arterial grave proximal, de un
embolismo arterio-arterial o de una combinación de ambos mecanismos. Representan
el 10% de los primeros ictus isquémicos y el 75% de los ictus tardíos en oclusiones de
la arteria carótida interna.
Los infartos frontera supratentoriales se pueden dividir en tres tipos en base a su
topografía:
1. Infartos frontera internos (corresponden a infartos de centro oval grandes):
afectan el territorio limítrofe entre las arterias perforantes con origen en el
polígono de Willis y las ramas leptomeníngeas de las arterias cerebrales
anterior, media y posterior.
2. Infartos frontera corticales anteriores: afectan el territorio limítrofe entre las
arterias cerebrales anterior y media. Se asocian con frecuencia a infartos
frontera internos.
3. Infartos frontera corticales posteriores: afectan el territorio limítrofe entre las
arterias cerebrales posterior y media.
El embolismo arterio-arterial o cardíaco es el mecanismo causal más frecuente en los
infartos frontera corticales, mientras que el hemodinámico probablemente asociado a
embolismo arterio-arterial de origen ateroesclerótico es el más frecuente en los infartos
frontera internos. Esta diferencia en el mecanismo causal de los infartos frontera, quizás
pueda atribuirse a la dificultad de diferenciar radiológicamente los infartos frontera
corticales aislados de los infartos territoriales parciales silvianos y a la variabilidad
individual en la distribución de los diferentes territorios arteriales.
Infartos agudos múltiples sincrónicos
Hasta un 17% de los pacientes con un ictus isquémico agudo muestran infartos agudos
múltiples en los estudios neuroradiológicos, especialmente cuando se obtienen
secuencias de difusión por RM. Éstos pueden tener varios mecanismos causales, que
pueden sugerirse en base a su patrón topográfico. Se han propuesto cinco tipos de
infartos agudos múltiples sincrónicos (IAMS):
9
• Tipo I: IAMS de circulación anterior uni-hemisféricos: corresponden a infartos que
afectan de forma fragmentada un único hemisferio cerebral. Son los más
frecuentes (44%) y en la mayoría de casos son infartos uni-territoriales (afectan
exclusivamente el territorio de la ACM). Se producen como consecuencia de una
fragmentación de un trombo en una única arterial proximal. El origen más
frecuente de estos émbolos proviene de una ateromatosis carotídea o silviana, o
de una disección carotídea (émbolos de la falsa luz). Otra de las situaciones que
se debe tener en cuenta es la posible fragmentación de un trombo tras
tratamiento fibrinolítico o tras procedimientos diagnósticos o recanalizadores
intraarteriales.
• Tipo II: IAMS de circulación anterior bi-hemisféricos. Corresponden al 21% de los
IAMS. Son por definición infartos multi-territoriales cuyo mecanismo causal más
frecuente es la enfermedad aterotrombótica seguida de la cardioembólica.
También deben considerarse causas menos frecuentes como estados de
hipercoagulabilidad
(coagulación
intravascular
diseminada,
púrpura
trombocitopénica trombótica), y la enfermedad de pequeño vaso (IAMS
lacunares). Las variaciones anatómicas del polígono de Willis pueden causar
este tipo de IAMS. Así, en la hipoplasia del segmento A1 de la arteria cerebral
anterior (10-20% de sujetos), la migración de émbolos desde una lesión
carotídea contralateral puede producir infartos que afectan los territorios irrigados
por las arterias cerebrales media y anterior homolaterales a la lesión carotídea, y
el de la arteria cerebral anterior contralateral.
• Tipo III: IAMS que afectan exclusivamente la circulación posterior. Corresponden
al 23% de los IAMS y pueden ser uni o multi-territoriales. El mecanismo causal
más frecuente es la enfermedad ateroesclerótica vértebro-basilar.
• Tipo IV: IAMS que afectan tanto la circulación anterior como la posterior.
Representan el 12% de los IAMS y el mecanismo causal más frecuente es el
embolismo de origen cardíaco o del arco aórtico. Un posible mecanismo
aterotrombótico debe sin embargo considerarse en pacientes que presenten un
origen fetal de la arteria cerebral posterior (15-25% de sujetos) o una
10
persistencia de la arteria comunicante posterior, en cuyo caso el material
embólico con origen en la arteria carótida interna puede producir infartos
sincrónicos que afectan unilateralmente territorios dependientes tanto de la
circulación anterior (arterias cerebrales anterior y media) como posterior (arteria
cerebral posterior).
Referencias
1. Caplan LR, Wityk RJ, Glass TA, Tapia J, Pazdera L, Chang HM, Teal P,
Dashe JF, Chaves CJ, Breen JC, Vemmos K, Amarenco P, Tettenborn B,
Leary M, Estol C, Dewitt LD, Pessin MS. New England Medical Center
Posterior Circulation registry. Ann Neurol. 2004; 56:389-98.
2. Erro ME, Gállego J, Herrera M, Bermejo B. Isolated pontine infarcts:
etiopathogenic mechanisms. Eur J Neurol. 2005;12:984-8.
3. Jung JM, Kwon SU, Lee JH, Kang DW. Difference in infarct volume and
patterns between cardioembolism and internal carotid artery disease: focus
on the degree of cardioembolic risk and carotid stenosis. Cerebrovasc Dis.
2010;29:490-6
4. Kameda W, Kawanami T, Kurita K, Daimon M, Kayama T, Hosoya T, Kato T;
Study Group of the Association of Cerebrovascular Disease in Tohoku.
Lateral and medial medullary infarction: a comparative analysis of 214
patients. Stroke. 2004;35:694-9.
5. Kang SY, Kim JS. Anterior cerebral artery infarction: stroke mechanism and
clinical-imaging study in 100 patients. Neurology. 2008;70:2386-93.
6. Klein IF, Lavallée PC, Touboul PJ, Schouman-Claeys E, Amarenco P. In vivo
middle cerebral artery plaque imaging by high-resolution MRI. Neurology.
2006;67:327-9.
7. Lee LJ, Kidwell CS, Alger J, Starkman S, Saver JL. Impact on stroke subtype
diagnosis of early diffusion-weighted magnetic resonance imaging and
magnetic resonance angiography. Stroke 2000;31:1081-9
8. Mangla R, Kolar B, Almast J, Ekholm SE. Border zone infarcts:
pathophysiologic and imaging characteristics. Radiographics. 2011;31:120114.
9. Micheli S, Agnelli G, Palmerini F, Caso V, Venti M, Alberti A, Biagini S,
Paciaroni M. Need for extensive diagnostic work-up for patients with lacunar
stroke.J Neurol. 2008; 255:637-42.
10. Nah HW, Kang DW, Kwon SU, Kim JS. Diversity of single small subcortical
infarctions according to infarct location and parent artery disease: analysis
of indicators for small vessel disease and atherosclerosis. Stroke
2010;41:2822-7.
11
11. Roh JK, Kang DW, Lee SH, Yoon BW, Chang KH. Significance of acute
multiple brain infarction on diffusion-weighted imaging. Stroke 2000;31:68894.
12. Rovira A, Grivé E, Rovira A, Alvarez-Sabin J. Distribution territories and
causative mechanisms of ischemic stroke. Eur Radiol 2005;15:416-26
13. Sato S, Toyoda K, Matsuoka H, Okatsu H, Kasuya J, Takada T, Shimode A,
Uehara T, Naritomi H, Minematsu K. Isolated anterior cerebral artery
territory infarction: dissection as an etiological mechanism. Cerebrovasc Dis.
2010;29:170-7.
14. Yonemura K, Kimura K, Minematsu K, Uchino M, Yamaguchi T. Small
centrum ovale infarcts on diffusion-weighted magnetic resonance imaging.
Stroke. 2002;33:1541-4.
15. Yong SW, Bang OY, Lee PH, Li WY. Internal and cortical border-zone
infarction: clinical and diffusion-weighted imaging features. Stroke.
2006;37:841-6.
16. Wartenberg KE. Malignant middle cerebral artery infarction. Curr Opin Crit
Care. 2012 Apr;18(2):152-63.
Eur Radiol (2005) 15: 416–426
DOI 10.1007/s00330-004-2633-5
A. Rovira
E. Grivé
A. Rovira
J. Alvarez-Sabin
Received: 30 June 2004
Accepted: 13 December 2004
Published online: 19 January 2005
# Springer-Verlag 2005
A. Rovira (*) . E. Grivé . A. Rovira .
J. Alvarez-Sabin
Hospital Vall d’Hebron, Unidad de
Resonancia Magnetica,
Passeig Vall d’Hebron 119-129,
08035 Barcelona, Spain
e-mail: [email protected]
NEURO
Distribution territories and causative
mechanisms of ischemic stroke
Abstract Ischemic stroke prognosis,
risk of recurrence, clinical assessment, and treatment decisions are
influenced by stroke subtype (anatomic distribution and causative
mechanism of infarction). Stroke
subtype diagnosis is better achieved
in the early phase of acute ischemia
with the use of multimodal MR
imaging. The pattern of brain lesions
as shown by brain MR imaging can
be classified according to a modified
Oxfordshire method, based on the
anatomic distribution of the infarcts
into six groups: (1) total anterior
circulation infarcts, (2) partial anterior
circulation infarcts, (3) posterior circulation infarcts, (4) watershed infarcts, (5) centrum ovale infarcts, and
(6) lacunar infarcts. The subtype of
stroke according to its causative
mechanism is based on the TOAST
Introduction
Ischemic stroke prognosis, risk of recurrence, clinical assessment, and treatment decisions are influenced by stroke
subtype. Nevertheless, treatment decisions are often made
before an extensive, time-consuming evaluation to identify
a likely diagnosis is completed. Therefore, early classification of ischemic stroke subtype is of substantial practical
clinical value. The most widely used methods for stroke
subtype classification are the Oxfordshire Community
Stroke Project and the TOAST (Trial of ORG 10172 in
Acute Stroke Treatment) method.
In 1991 the Oxfordshire Community Stroke Project (OCSP)
proposed four subgroups of cerebral infarction (Table 1)
based solely on presenting signs and symptoms [1]. This
method, which classifies stroke into
five major etiologic groups: (1) largevessel atherosclerotic disease, (2)
small-vessel atherosclerotic disease,
(3) cardioembolic source, (4) other
determined etiologies, and (5) undetermined or multiple possible etiologies. The different MR imaging
patterns of acute ischemic brain
lesions visualized using diffusionweighted imaging and the pattern of
vessel involvement demonstrated with
MR angiography are essential factors
that can suggest the most likely
causative mechanism of infarction.
This information may have an impact
on decisions regarding therapy and
the performance of additional diagnostic tests.
Keywords Diffusion . MRI . Stroke
method has the ability to predict the prognosis and shows
good correlation with the underlying pathophysiology and
imaging findings on cranial computed tomography (CT)
[2].
The TOAST method is a set of guidelines developed for
prospectively classifying ischemic strokes into specific subtypes, based mainly on the mechanism of infarction [3, 4].
Stroke patients are classified into five major etiologic/pathophysiologic groups (Table 2).
With the widespread use of diffusion-weighted MR imaging (DWI) and MR angiography (MRA) in the acute
stage of ischemic stroke, accurate early diagnosis of ischemic stroke subtype can be better achieved [5]. This information can be helpful for establishing the most likely
417
Table 1 Topographic clinical pattern of brain infarction (Oxfordshire method)
1. Lacunar infarcts (LACI) Acute stroke that includes one of the
major recognized lacunar syndromes:
pure motor, sensory, or sensorimotor
strokes, ataxic hemiparesis, and dysarthria (clumsy hand syndrome)
2. Total anterior circula- Clinical syndrome in which there is
tion infarcts (TACI)
ischemia in both the deep and superficial territories of the middle cerebral
artery (higher cerebral dysfunction such
as dysphasia, dyscalculia, visuospatial
disorder; homonymous visual field defect; and ipsilateral motor and/or sensory deficit of at least two areas of the
face, arm, and leg)
3. Partial anterior circula- Clinical syndrome that includes only
tion infarcts (PACI)
two of the three components of the
TACI syndrome, with higher cerebral
dysfunction alone, or with more restricted sensorimotor deficit than those
classified as LACI
4. Posterior circulation in- Clinical syndrome that includes ipsifracts (POCI)
lateral cranial nerve palsy with contralateral motor and/or sensory deficit;
bilateral motor and/or sensory
deficit; disorder of conjugate eye
movement; cerebellar dysfunction
without ipsilateral long-tract deficit
(i.e., ataxic hemiparesis); or isolated
homonymous visual field defect
mechanisms of ischemia and the risk of clinical progression, and for initiating the most appropriate therapy.
This review article is divided into three parts. The first
addresses the topographic patterns of brain infarction, the
second is devoted to the mechanisms implicated in the
genesis of multiple synchronous acute brain infarcts, and
the third part reviews the various stroke categories on the
basis of their causative mechanisms.
ditions that govern flow in leptomeningeal anastomoses
connecting the different arterial territories [6]. Despite this
variability, brain imaging can accurately locate an ischemic
stroke lesion in a specific vascular distribution in the majority of cases [7–10].
Arterial cerebral circulation can be divided into two
systems: (1) the leptomeningeal (also known as superficial
or pial) artery system; and (2) the perforating (or deep
perforating) artery system (Table 3).
Leptomeningeal artery system
The leptomeningeal arteries comprise the terminal branches
of the cerebral and cerebellar arteries, which penetrate the
cortex and subjacent white matter. Infarcts within the territories irrigated by these arteries are often described as
territorial infarcts.
Territorial anterior infarcts
Territorial anterior infarcts, mostly related to the middle
cerebral artery (MCA) territory, can be divided into large
and limited types.
Large infarcts, defined as those covering at least two of
the three MCA territories (deep, superficial anterior, and
superficial posterior), show a high frequency of clinical
deterioration, a minimum chance of good outcome, and a
high mortality rate. Large MCA infarctions are associated
with cardioembolism, internal carotid artery (ICA) occlusion, and ICA dissection. In patients with large infarcts
without ICA occlusion, the frequency of cardioembolic
Table 3 Topographic radiologic pattern of brain infarction
Leptomeningeal artery
system
Topographic pattern of brain infarcts
The boundaries between vascular distributions are determined by anatomic variations and by hemodynamic conTable 2 Stroke categories (TOAST method)
1
2
3
4
5
Large-vessel disease
Small-vessel disease
Cardioembolism
Other etiology
Undetermined or multiple possible etiologies
Deep perforator artery
system
Territorial anterior circulation infarcts
Large
Malignant
Limited
Territorial posterior circulation
infarcts
Large territorial
Small or end zone infarcts
Brainstem infarcts
Centrum ovale infarcts
Large
Small
Watershed infarcts
Internal
Cortical anterior
Cortical posterior
Lacunar infarcts
418
disease is clearly higher than in large infarcts with ICA
occlusion or limited infarcts without ICA occlusion [11].
Malignant MCA infarction refers to life-threatening (80%
associated mortality), complete or almost complete MCA
infarction. This type of infarction occurs in up to 10% of all
stroke patients. The main cause of death is severe post-ischemic brain edema leading to raised intracranial pressure.
The clinical course is uniform, with clinical deterioration
developing within the first 2 to 3 days after stroke. DWI in the
early phase of large territorial anterior infarction is an accurate
method for predicting malignant MCA infarction (lesion
volume >145 cm3) [12] in patients with persistent arterial
occlusion and signs of total anterior circulation infarction.
Early detection may be important since treatment for these
large infarcts, such as hypothermia and/or hemicraniectomy
can significantly reduce mortality [13].
Limited infarcts, covering only one of the three MCA
territories, show a very low frequency of clinical deterioration. The mechanism of infarction in these cases is either
cardioembolism or large-artery atherosclerosis in equal
numbers. The lower incidence of cardioembolism in limited
MCA infarcts as compared to large infarcts can be explained by the fact that cardiac thrombi are generally larger
than thrombi of the large vessels [2] (Fig. 1).
Territorial posterior infarcts
Fig. 1 Diffusion-weighted MR imaging in anterior choroidal artery
(AChA) infarcts. Right acute lacunar infarct limited to the AChA
territory with no significant stenosis in an ipsilateral large artery,
probably related to small-vessel disease (A). Acute right AChA territory infarct associated with other ipsilateral internal carotid artery
infarcts due to internal carotid artery dissection (arrow) (B).
Centrum ovale infarcts
With the use of MR imaging, posterior circulation infarcts
can be diagnosed and their topography delineated with
high sensitivity. Infarcts are recognized in the territory of
the posterior inferior (PICA), anterior inferior (AICA), and
superior (SCA) cerebellar arteries and their branches, and
in the territory of the posterior cerebral arteries (PCA) [8].
Large-vessel atherosclerosis of the extracranial and intracranial vertebrobasilar arteries, has been demonstrated
angiographically in more than two thirds of patients with
cerebellar infarction, and in situ branch artery disease in
almost one fifth of these patients. Proximal disease of the
vertebral artery is the most common feature in large-artery
disease, leading to PICA, SCA, and PCA infarcts. The
vessels most frequently affected by intraarterial embolism
are the intracranial vertebral artery (leading to PICA
infarcts) and the distal basilar artery (leading to SCA and
PCA infarcts). Thrombus originating from proximal vertebral artery disease never occludes the intracranial vertebral artery, but it can affect the PICA, AICA, and SCA.
Therefore, vascular imaging in patients with atherothrombotic cerebellar infarcts must assess the proximal vertebral
artery (V1) [14].
Clinical deterioration in posterior circulation infarcts is
associated with severe brain atrophy (suggesting longstanding hypoperfusion), and significant stenosis in the vertebrobasilar arteries. This feature implies that large-vessel
disease plays an important role in clinical worsening in
posterior circulation infarcts [2].
Small cerebellar infarcts (<2 cm) are frequently recognized with MR imaging. These small infarcts were thought
to affect the boundary zone between various territories
(nonterritorial infarcts), but in fact, they seem to be very
small territorial infarcts resulting from involvement of
small distal arteries. Therefore, small cerebellar infarcts
correspond to “end zone” infarcts, with embolic or local
arterial disease as the mechanism of infarction in the majority of cases; a low-flow hemodynamic state is the likely
cause of infarction in only a minority of patients.
Territorial and nonterritorial (small) cerebellar infarcts
are essentially the same, and it is likely that their extent
and location simply depend on the size of the embolus
causing the infarct [15, 16].
Brainstem infarcts may be related to large-vessel disease
(stenosis or occlusion) affecting the vertebral and basilar
arteries or their main branches. In this situation, brain MR
usually shows additional infarcts involving the territories
irrigated by the cerebellar and posterior cerebral arteries.
The centrum ovale is the central white matter of the cerebral
hemispheres, including the most superficial part of the
corona radiata and the long associated fasciculi. The cen-
419
trum ovale is supplied by long (2 to 5 cm) noninterdigitating
medullary arteries that perforate it and course toward the
upper part of the lateral ventricles. At the deeper part of
the corona radiata the medullary branches tend to form an
area of junction with the deep perforating branches of the
MCA and the AChA. Centrum ovale infarcts are those
limited to the territory of the medullary branches without
accompanying involvement of the cortex or deep perforator territory [17].
Centrum ovale infarcts can be large and small.
Large centrum ovale infarcts (>1.5 cm) affect more than
one medullary branch. A hemodynamic mechanism related
to severe ipsilateral internal carotid or MCA disease may
be the leading cause. In this situation, the infarct affects the
area of the internal border zone, between the deep perforators and superficial medullary territories of the MCA
(internal border zone infarcts). However artery-to-artery
embolism and cardioembolism cannot be ruled out in some
patients.
Small centrum ovale infarcts (<1.5 cm) involve only one
medullary branch. Small infarcts were thought to be related
to small-vessel disease involving the medullary branches,
in a manner similar to lacunar infarction. In fact, the neurologic picture of small infarct of the centrum ovale is
consistent with a so-called lacunar syndrome, although the
motor or sensory distribution pattern is less often complete
(face, arm, and leg) than partial. However, recent studies
have shown that in a significant percentage of patients,
small centrum ovale infarcts are associated with largevessel and heart disease, and should be distinguished from
the more common lacunar infarcts [18]. Identification of
subsidiary small acute infarcts in addition to an acute small
infarct in the centrum ovale on DWI suggests an embolic
mechanism [17].
Watershed infarcts
Watershed infarcts (WIs) are ischemic lesions that occur at
the junction between two or three arterial territories and
Fig. 2 Watershed infarcts. Diffusion-weighted MR images
showing the classical pattern of
anterior cortical (A), posterior
cortical (B) and internal
(C) watershed infarcts.
account for approximately 10% of ischemic strokes. The
pathogenesis of WIs is controversial. It may involve various mechanisms such as systemic hypotension, severe
arterial stenosis or ICA occlusion, microemboli, or a combination of these. Watershed infarcts account for 72% of
delayed strokes in patients with ICA occlusion, but are
rarely the initial manifestation of ICA occlusion (5%) [19].
Recent data indicate that WIs are often explained by a
combination of two inter-related processes: hypoperfusion
and embolization. In fact, severe ICA occlusive disease and
cardiac surgery cause both embolization and decreased
brain perfusion. This decreased perfusion might alter blood
flow currents, encouraging microemboli to reach recipient
blood vessels with the least effective blood flow. Moreover,
microemboli that reach a border zone area with decreased
blood flow are difficult to wash out [20].
Two types of vascular border zone areas exist within the
cerebral hemispheres: the cortical and the internal. Cortical
border zone areas are located between the cortical supply
of the ACA and MCA (anterior cortical border zone), and
between the MCA and PCA (posterior cortical border
zone). Internal border zone areas are located between the
ACA (anterior cerebral artery), MCA, and PCA, and the
area supplied by the Heubner, lenticulostriate, and ACh
arteries (Fig. 2).
Purely anterior cortical WIs are very rare, as in most
cases they are associated with internal border zone infarcts. Posterior cortical WIs are frequently difficult to
differentiate from limited territorial infarcts affecting the
posterior division of the MCA. Embolism, not distal field
perfusion failure, is the predominant stroke mechanism in
this type of WI.
Internal border zone infarcts, commonly associated with
severe ICA stenosis, are larger than lacunar infarcts within
the vascular territory of the deep perforators. In some cases
it is difficult to distinguish internal border zone infarcts
from centrum ovale infarcts within the territory irrigated by
the medullary branches of the MCA. The presence of two or
more lesions, appearing as a chain of round infarcts along
the internal vascular border zone, suggests an internal bor-
420
der zone infarct. Lesions in the internal border zone are
mainly attributed to the effect of hemodynamic impairment
caused by severe stenosis or occlusion of the ICA or MCA.
Nevertheless, some studies have suggested an embolic mechanism for both cortical watershed and internal border
zone infarcts [21].
Watershed infarcts involving more than one of the
border zone areas in a single hemisphere are mostly related
to severe ICA stenosis or occlusion. Bilateral watershed
infarcts are typically related to a profound global reduction
in perfusion pressure (hypoxia, hypovolemia) or to diffuse
cerebral vessel disease (sickle-cell disease).
The perforating (or deep perforating) artery system
The perforating arteries arise from the arterial circle of
Willis, the AChA, and the basilar artery, perforating the
brain parenchyma as direct penetrators and supplying the diencephalon (thalamus, hypothalamus, subthalamus, and epithalamus), basal ganglia, internal capsule, and brainstem [10].
Lacunar infarcts
The strict pathologic definition of a lacunar infarction (LI)
is a small (<1.5 cm in diameter), fluid-filled cavity representing the healed stage of a small deep infarct, which
was likely due to occlusion of a single penetrator artery
arising from the large arteries of the circle of Willis or
from the basilar artery. The most frequently affected perforating arteries include the lenticulostriate, the thalamoperforate and the perforators arising from the AChA.
Thus, LI can be located deep within the cerebral hemispheric white matter, the upper two thirds of the basal
ganglia, the internal capsule, the thalamus or the paramedian and lateral regions of the brainstem. Brainstem LI are
mainly found in the paramedian region of the pons, which is
supplied by long arterioles (midline and anteromedial
perforators) arising from the basilar artery. The medulla and
midbrain are supplied by short arterioles, which are less
vulnerable to aging and hypertension, and as a consequence
LI are very uncommon in these locations.
The maximum size of 15 mm is probably true for LI in
the chronic stage. In fact, most of them have a diameter
<10 mm, but this dimension does not apply in the acute
phase, when cellular swelling and extracellular edema can
produce LI larger than 15 mm in diameter.
Most first-ever symptomatic LI are located in the area
supplied by the AChA [9, 22], while multiple, asymptomatic LI are mainly located within the territory irrigated
by perforating arteries arising from the MCA or ACA.
Most LI are asymptomatic. Symptoms are related to size
(most lesions less than 200 μm in diameter are silent) and
location (LI in the posterior limb of the internal capsule or
in the pontine base are usually symptomatic, whereas
lesions in the basal ganglia tend to be silent).
Although most lacunar strokes appear to be a consequence of small-vessel disease (atherosclerosis or lipohyalinosis) [23], many of the other potential causes of
small-vessel occlusion rarely cause LI, such as infective or
immune vasculitis, artery-to-artery or cardiogenic embolism, arterial dissection, and in situ thrombosis due to a
variety of hypercoagulable states [24]. This non–smallvessel disease mechanism of LI is supported by the not
infrequent association of acute LI and superficial infarcts.
As a consequence, vascular imaging of the cervical and
intracranial arteries and a focussed search for a cardiac
source of the embolism is needed in first-ever lacunar
strokes. The detection of subsidiary infarctions in patients
presenting with a classic lacunar syndrome and often
diagnosed with intrinsic small-vessel disease (with a high
probability of excellent recovery, recommendation of antiplatelet agents for secondary prevention, and low priority
placed on extensive cardiac or arterial testing for other
causes of stroke), should prompt the physician to search
for an underlying embolic source and tailor a secondary
stroke prevention strategy to treat the underlying cause.
Embolic infarcts can present as a clinically well-defined
lacunar syndrome. However, the concept of embolic LI is
dubious for two main reasons: the low likelihood of an
embolus entering a vascular territory that receives such a
small proportion of cerebral blood flow, and the sharp
angle of the penetrating vessels arising from the parent
vessel, which makes it more likely for an embolus to be
directed toward the leptomeningeal arteries. However, as
compared to a leptomeningeal territory, the lack of collateral flow pathways in the deep perforating artery territories may make them more susceptible to infarction on
entry of a very small embolus. In fact, it has been suggested that a massive shower of emboli such as that occurring during cardiac and aortic operations, in cholesterol
embolization from ulcerated atheroma, and in paradoxical
fat or air embolism can produce LI.
Acute multiple brain infarction
Synchronous acute multiple brain infarcts (AMBIs) can
have various mechanisms of origin, which are suggested by
their topographic pattern. With the use of DWI, the different
types of AMBI can be easily identified [25, 26]:
(1) Internal watershed infarcts: multiple rosary-like infarcts
within border zone areas. Unilateral watershed infarcts
are usually related to ICA disease, whereas bilateral
ones are typically related to a profound overall reduction in perfusion pressure or to diffuse cerebral vascular disease.
(2) Multiple small cortical or subcortical infarcts within
the same arterial territory. This type of AMBI is attri-
421
buted to fragmentation of an embolus near its origin or
located within a major proximal intracranial artery.
Most of these infarcts are found within one cerebral
hemisphere in the anterior circulation.
(3) Multiple small infarcts attributable to multiple arteryto-artery thromboembolic material (located in one or
more major arterial territories, depending on the arterial
anatomy). Sometimes these infarcts are located in two
hemispheres and in both the anterior and posterior circulation. Acute multiple brain infarcts exclusively affecting the posterior circulation are, in most cases,
related to large-artery atherosclerosis. The anatomic
variations that may explain AMBI include (1) posterior
communicating artery (PCoA) originating from the
ICA (fetal-type PCA), which explains the simultaneous infarcts in the anterior and posterior cerebral
artery territory (25% of cerebral hemispheres); (2)
PCoA patency (67% of anatomic dissections), explaining multiple infarcts in both the anterior and posterior
circulation; and (3) AMBI in the territories of both
ACAs when a single artery supplies the two medial
aspects of the hemispheres, occurring in 18% of the
normal population.
(4) Multiple infarcts located in one or more major arterial
territories of the anterior and/or posterior circulation
produced from embolic sources proximal to the cervical arteries (heart or aortic arch), not attributable to
anatomic variations of the cervicocranial arterial vessels. The pattern of multiple, small and large bihemispheric AMBIs is especially frequent in nonbacterial
thrombotic endocarditis (marantic endocarditis).
(5) Multiple simultaneous deep perforators. Most of these
cases are related to bilateral, simultaneous small-artery
occlusion.
Cardioembolism can be the mechanism of infarcts in
groups 2, 3, and 4, although it is much more frequent in
group 4. Nevertheless, bilateral carotid stenosis or occlusion can also be associated with acute infarcts in both
cerebral hemispheres.
The main causes of AMBI in one hemisphere in the
anterior circulation are MCA and ICA disease (75%).
Although the factors that determine contemporary infarcts in small-vessel occlusion or severe bilateral largevessel disease are unknown (groups 3 and 5), it is believed
that erytrocytosis (elevated primary or secondary hematocrit) and increased serum fibrinogen, may be important
contributory factors [25]. In fact, these factors are significantly associated with bilateral cerebral infarction in
patients with large-artery atherosclerosis or small-artery
occlusion. Other possible explanations for AMBI located in
different vascular territories include bilateral or unilateral
watershed infarctions, or diffuse thrombotic or inflammatory processes, such as thrombotic thrombocytopenic purpura, granulomatous angiitis, and anticardiolipin syndrome,
which lead to multiple small-vessel occlusions within a
short period of time.
Stroke categories
The subtype of stroke according to its causative mechanism (TOAST) is based on risk factor profiles, clinical
features, and the results of diagnostic tests [3, 4].
The TOAST algorithm classifies patients with ischemic
stroke into five major etiologic and pathophysiologic
groups: large-vessel atherosclerotic disease, small-vessel
atherosclerotic disease, cardioembolism, other etiologies,
and undetermined or multiple possible etiologies.
Examining responses to acute treatment in each one of
these subgroups of stroke mechanisms is clinically important; therefore, highly accurate early stroke subtyping
is needed. The sensitivity and positive predictive value of
the initial TOAST diagnosis of large- and small-vessel
disease improves considerably with the combined use of
DWI and MRA techniques [5].
Large-vessel atherosclerotic disease
Large-vessel atherosclerosis represents about 13% of all
patients with a first-ever stroke.
Cortical or cerebellar lesions and brainstem or subcortical hemispheric infarcts greater than 1.5 cm in diameter
on brain imaging are considered to be potential large-artery
disease strokes. Supportive evidence by vascular imaging
of more than 50% stenosis in an appropriate intracranial
or extracranial artery (presumably due to atherosclerosis)
is needed. Embolic (artery-to-artery) and hemodynamic
mechanisms are the cause of stroke in these patients. The
coexistence of both mechanisms has been postulated.
Five patterns of ischemic lesions can be differentiated in
patients with acute stroke and large-vessel disease [27, 28]
(Fig. 3).
Cortical territorial infarction
Cortical territorial infarcts are ischemic lesions involving
the cerebral cortex and subcortical structures in one or
more major cerebral artery territories. Almost half of the
patients with ICA occlusion have territorial infarction.
However about 20% of strokes in the territory of a highgrade symptomatic ICA are cardioembolic or lacunar.
This pattern can be subclassified into three forms: (1)
limited MCA infarction in occlusions of a distal MCA
branch or the proximal MCA, associated with effective
collateral circulation; (2) large MCA infarction, frequently
related to large emboli that proximally occlude the MCA in
the absence of an efficient collateral system, or to occlusions of the distal ICA with a partially effective collateral
422
Fig. 3 Different patterns of
cortical territorial infarcts within
the internal carotid artery (ICA)
territory demonstrated with diffusion-weighted MR imaging
and MR angiography. A Limited
left middle cerebral artery
(MCA) infarction due to occlusion of the proximal MCA.
B Complete right ICA infarction
due to occlusion of the ICA.
C Large left MCA infarction
due to occlusion of the MCA.
D Subcortical right MCA infarction due to MCA occlusion
with small fragmented subcortical and cortical subsidiary
infarcts. E Fragmented right
cortical MCA infarction due to
severe MCA stenosis (arrow).
F Small fragmented right infarctions in the left MCA territory due to severe stenosis at the
origin of the right ICA.
423
system; and (3) complete infarcts involving two major ICA
cerebral artery territories in distal occlusions of the ICA
without an effective collateral system.
Subcortical infarction
Subcortical infarcts are ischemic lesions in the territory
of the deep perforating branches arising from the distal
ICA or MCA trunk in proximal occlusions of the MCA
or ICA in the presence of patent collaterals. Additional
fragmented small cortical or subcortical infarctions can
be also identified.
Cortical territorial infarction with fragmentation
Large ischemic cortical lesions with additional smaller
cortical or subcortical lesions due to partial fragmentation
of an embolus fall into the category of cortical infarction
with fragmentation.
Fragmented infarction
Fragmented infarcts are defined as several small, disseminated lesions sprinkled randomly in the cortical ICA regions due to multiple emboli or the break-up of an embolus.
Fragmented infarctions are more common in moderate ICA
stenosis or in fragmentation of a lodged embolus. In the
latter case, there is often no evidence of stenosis or occlusion in the intracranial arteries (resolved embolism).
Watershed infarction
The pathogenesis of watershed infarctions is controversial.
The leading mechanism is believed to be critical ICA
stenosis or occlusion, which may or may not be associated
with transient hypoperfusion. In fact, 75% of patients with
WI have high-grade ICA stenosis or occlusion associated
with hemodynamically significant heart disease, increased
hematocrit, or acute hypotension. Conversely, 50% of patients with high-grade or subtotal ICA stenosis have watershed infarcts. Atherosclerotic disease of the MCA may also
cause watershed infarcts. For this reason, in addition to the
extracranial vessel, cerebrovascular investigation in these
patients should include the large intracranial vessels.
tension seems to be the main etiology of these pathologic
events, but a variety of other conditions such as aging,
hypoperfusion, generalized atherosclerosis, diabetes, and
orthostatic hypotension can contribute to the brain microcirculation compromise. In fact, in a significant proportion
of patients, small-vessel disease is identified in normotensive, nonelderly, nondiabetic individuals.
Atherosclerosis
Atherosclerosis of the small penetrator vessels or microatheromatosis is the leading cause of small-artery disease.
Atheroma plaques are localized in the proximal perforating arteries (microatheroma), in the origin of the penetrator
artery (junctional atheroma), or in the parent artery on the
circle of Willis (mural atheroma). Mural atheroma is particularly frequent in the basilar artery, producing infarcts
limited to its pontine perforating branches.
The atheroma plaques result in occlusion of the proximal
segment of the large penetrating arteries (300–900 μm) and
usually lead to single, large, frequently symptomatic LI
[29]. This type of small-vessel disease, which is not so
strongly related to hypertension, seems to predominantly
involve the penetrator vessels arising from the anterior
choroidal artery. Radiologic studies in patients with a firstever lacunar stroke of this type commonly show no additional asymptomatic infarcts or leukoaraiosis (Fig. 4a).
Lipohyalinosis
Lipohyalinosis, a vascular disease associated with longlasting, severe hypertension, is the second small-vessel
lesion of relevance in lacunar infarction. It is a destructive
lesion of the small penetrating arteries (<200 μm) that
leads to small LI, which are commonly asymptomatic and
located predominantly in the striatocapsule and thalamus.
Leukoaraiosis and old asymptomatic LI are commonly
seen on brain imaging in these patients (Fig. 4b).
The mechanism of infarction seems to be related to
occlusive thrombosis (perhaps exacerbated by a hypercoagulable state) or to non-occlusive poststenotic hypoperfusion. Patients with this type of small-vessel disease have
a better outcome and a smaller prevalence of large-vessel
cerebral disease and coronary disease than patients with
the atherosclerotic type.
Cardioembolism
Small-vessel disease (small-artery occlusion)
Small-vessel disease is the cause of about 25% of all firstever strokes. The most frequent pathologic events related to
small-vessel disease are atherosclerosis and lipohyalinosis
limited to the small penetrator vessels [23]. Chronic hyper-
Cardiogenic embolism is responsible for about 15–27% of
all first-ever strokes. The incidence is higher in patients
under 45 years old, primarily because of the lower incidence of atherosclerotic disease in this age group. About
16% of ischemic strokes are associated with atrial fibril-
424
Table 4 Sources of risk for cardioembolism
Higher risk sources for
cardioembolism
Lower risk sources for
cardioembolism
Fig. 4 Acute LI (Fast-Flair and diffusion-weighted MR images).
A Acute left internal capsule (territory of the anterior choroidal artery)
infarct with no additional infarcts or leukoaraiosis, probably related to
microatherosclerosis. B Acute left thalamic lacunar infarct associated
with small chronic LI and dilated Virchow-Robin spaces, suggesting
small-vessel atherosclerotic disease due to lipohyalinosis.
lation, and 10% are probably due to embolism from an
atrial appendage thrombus, with the remainder caused by
other stroke mechanisms [30]. Cerebral infarction in atrial
fibrillation tends to be large and severely disabling [31]. A
possible or probable diagnosis of cardioembolic stroke
requires the identification of at least one cardiac source for
an embolus (high-risk or medium-risk sources) (Table 4).
Evidence of a previous transient ischemic attack or stroke
in more than one vascular territory or systemic embolism
supports a clinical diagnosis of cardiogenic stroke.
On brain imaging, large cortical territorial infarction
should suggest a cardioembolic mechanism, particularly if
it is not associated with ICA occlusion. The median volume
of infarcts caused by cardiogenic embolism is more than
twice the median volume of infarcts caused by artery-toartery embolism [31].
Although it has been suggested that simultaneous acute
infarction indicates a cardioembolic mechanism, in the
majority of cases they are not caused by a proximal embolism from the heart or aortic arch, but instead by arteryto-artery embolism or fragmentation of a proximal artery
embolus.
Atrial fibrillation
Mural thrombus associated with acute
myocardial infarction
Prosthetic heart valve
Dilated cardiomyopathy
Bacterial endocarditis
Rheumatic mitral stenosis
Ascending aorta atheroma (≥4 mm in
size)
Intracardiac thrombus
Spontaneous left atrial echo contrast
Left ventricular aneurysm or large area
of dyskinesia
Nonbacterial (marantic) endocarditis
Sick sinus syndrome
Calcified aortic stenosis
Patent foramen ovale or atrial septal
defect
Atrial septal aneurysm
Mitral annulus calcification
Ventricular septal defect
Mitral valve prolapse
Other etiologies
Only 2% of all patients with a first-ever stroke fall into
the other etiology category. The lesion can have any size
or location. To classify a stroke under this category, cardiac sources of embolism and large-artery atherosclerosis
should be excluded. These unusual mechanisms of stroke
include nonatherosclerotic, nonhypertensive vascular diseases (Moya-Moya disease, craniocervical arterial dissection, and primary and systemic vasculitis), migraine,
hypercoagulable states, hematologic disorders, stroke after
catheter angiography, and sporadic or genetically determined small-vessel occlusion such as cerebral autosomal
dominant arteriopathy (CADASIL) and Fabry’s disease.
These rare forms of small-vessel occlusion cannot be differentiated radiologically from the classical atherosclerotic
and hypertensive forms of small-vessel disease.
Undetermined etiology or multiple possible etiologies
Strokes classified as having undetermined or multiple possible etiologies must possess one of the following conditions:
(1) No cause found despite extensive assessment.
(2) Most likely cause could not be determined because
more than one plausible cause was found (e.g., atrial
fibrillation or lacunar infarct associated with >50%
symptomatic large vessel stenosis).
425
This type of stroke represents about 35% of all patients
with a first-ever stroke. However, this percentage can vary
considerably, since in some cases an extensive diagnostic
evaluation is performed (ECG, Duplex, MRI/MRA, transcraneal Doppler ultrasound, transesophageal echocardiography, laboratory tests for coagulation factors, proteins C
and S, antithrombin III, and various autoantibodies), whereas in others the evaluation is cursory.
Conclusion
lesion and the presence of significant arterial stenosis or
occlusion. Multimodal MR imaging facilitates the achievement of these diagnostic goals, improving the accuracy of
early ischemic stroke subtype identification. The various
MRI patterns of acute brain ischemia (topography, size,
and multiplicity) visualized using DWI, the pattern of
vessel involvement demonstrated with MR angiography,
and the presence of previous ischemic lesions detected with
conventional MRI, are essential factors that can suggest the
most likely mechanisms of origin. This information may
have an impact on decisions regarding therapy and the
performance of additional diagnostic tests.
The goal of imaging in the acute phase of ischemic stroke
is to identify the location and extension of the relevant
References
1. Bamford J, Sandercock P, Dennis M
et al (1991) Classification and natural
history of clinically identifiable subtypes of cerebral infarction. Lancet
337:1521–1526
2. Tei H, Uchiyama S, Ohara K,
Kobayashi M, Uchiyama Y, Fukuzawa
M (2000) Deteriorating ischemic stroke
in 4 clinical categories classified by the
Oxfordshire Community Stroke Project. Stroke 31:2049–2054
3. Adams HP, Bendixen BH, Kappelle LJ
et al (1993) Classification of subtype of
acute ischemic stroke: definitions for
use in a Multicenter Clinical Trial.
Stroke 24:35–41
4. Kolominsky-Rabas PL, Weber M,
Gefeller O, Neundoerfer B,
Heuschmann PU (2001) Epidemiology of ischemic stroke subtypes according to TOAST criteria: incidence,
recurrence, and long-term survival in
ischemic stroke subtypes: a populationbased study. Stroke 32:2735–2740
5. Lee LJ, Kidwell CS, Alger J et al
(2000) Impact on stroke subtype diagnosis of early diffusion-weighted magnetic resonance imaging and magnetic
resonance angiography. Stroke
31:1081–1089
6. van der Zwan A, Hillen B, Tulleken
CA, Dujovny M, Dragovic L (1992)
Variability of the territories of the major
cerebral arteries. J Neurosurg 77:927–
940
7. Tatu L, Moulin T, Bogousslavsky J,
Duvernoy H (1998) Arterial territories
of the human brain: cerebral hemispheres. Neurology 50:1699–1708
8. Tatu L, Moulin T, Bogousslavsky J,
Duvernoy H (1996) Arterial territories
of human brain: brainstem and cerebellum. Neurology 47:1125–1135
9. Hupperts RM, Lodder J, Heuts-van
Raak EP, Kessels F (1994) Infarcts in
the anterior choroidal artery territory:
anatomical distribution, clinical syndromes, presumed pathogenesis and
early outcome. Brain 117:825–834
10. Takahashi S, Suzuki M, Matsumoto K,
Ishii K, Higano S, Fukasawa H,
Sakamoto K (1994) Extent and location
of cerebral infarcts on multiplanar MR
images: correlation with distribution of
perforating arteries on cerebral
angiograms and on cadaveric
microangiograms. Am J Roentgenol
163:1215–1222
11. Heinsius T, Bogousslavsky J, Van
Melle G (1998) Large infarcts in the
middle cerebral artery territory: etiology and outcome patterns. Neurology
50:341–350
12. Oppenheim C, Samson Y, Manai R,
Lalam T, Vandamme X, Crozier S,
Srour A, Cornu P, Dormont D,
Rancurel G, Marsault C (2000) Prediction of malignant middle cerebral
artery infarction by diffusion-weighted
imaging. Stroke 31:2175–2181
13. Georgiadis D, Schwarz S, Aschoff A,
Schwab S (2002) Hemicraniectomy and
moderate hypothermia in patients with
severe ischemic stroke. Stroke
33:1584–1588
14. Min WK, Kim YS, Kim JY, Park SP,
Suh CK (1999) Atherothrombotic cerebellar infarction: vascular lesion–MRI
correlation of 31 cases. Stroke
30:2376–2381
15. Amarenco P, Kase CS, Rosengart A,
Pessin MS, Bousser MG, Caplan LR
(1993) Very small (border zone) cerebellar infarcts: distribution, causes,
mechanisms and clinical features. Brain
116:161–186
16. Amarenco P, Levy C, Cohen A,
Touboul PJ, Roullet E, Bousser MG
(1994) Causes and mechanisms of
territorial and nonterritorial cerebellar
infarcts in 115 consecutive patients.
Stroke 25:105–112
17. Bogousslavsky J, Regli F (1992) Centrum ovale infarcts: subcortical infarction in the superficial territory of the
middle cerebral artery. Neurology
42:1992–1998
18. Yonemura K, Kimura K, Minematsu K,
Uchino M, Yamaguchi T (2002) Small
centrum ovale infarcts on diffusionweighted magnetic resonance imaging.
Stroke 33:1541–1544
19. Bogousslavsky J, Regli F (1986)
Borderzone infarctions distal to internal
carotid artery occlusion: prognostic
implications. Ann Neurol 20:346–350
20. Belden JR, Caplan LR, Pessin MS,
Kwan E (1999) Mechanisms and clinical features of posterior border-zone
infarcts. Neurology 53:1312–1318
21. Del Sette M, Eliasziw M, Streifler JY,
Hachinski VC, Fox AJ, Barnett HJ
(2000) Internal borderzone infarction: a
marker for severe stenosis in patients
with symptomatic internal carotid artery disease. For the North American
Symptomatic Carotid Endarterectomy
(NASCET) Group. Stroke 3:631–636
426
22. Boiten J, Lodder J, Kessels F (1993)
Two clinically distinct lacunar infarct
entities? A hypothesis. Stroke 24:652–
656
23. de Jong G, Kessels F, Lodder J (2002)
Two types of lacunar infarcts: further
arguments from a study on prognosis.
Stroke 33:2072–2076
24. Lodder J, Bamford JM, Sandercock PA,
Jones LN, Warlow CP (1990) Are
hypertension or cardiac embolism
likely causes of lacunar infarction?
Stroke 21:375–381
25. Roh JK, Kang DW, Lee SH, Yoon BW,
Chang KH (2000) Significance of acute
multiple brain infarction on diffusionweighted imaging. Stroke 31:688–694
26. Baird AE, Lovblad KO, Schlaug G,
Edelman RR, Warach S (2000) Multiple acute stroke syndrome: marker of
embolic disease? Neurology 54:674–
678
27. Min WK, Park KK, Kim YS, Park HC,
Kim JY, Park SP, Suh CK (2000)
Atherothrombotic middle cerebral artery territory infarction: topographic
diversity with common occurrence of
concomitant small cortical and subcortical infarcts. Stroke 31:2055–2061
28. Szabo K, Kern R, Gass A, Hirsch J,
Hennerici M (2001) Acute stroke
patterns in patients with internal carotid
artery disease: a diffusion-weighted
magnetic resonance imaging study.
Stroke 32:1323–1329
29. Arauz A, Murillo L, Cantu C,
Barinagarrementeria F, Higuera J
(2003) Prospective study of single and
multiple lacunar infarcts using magnetic resonance imaging: risk factors,
recurrence, and outcome in 175 consecutive cases. Stroke 34:2453–2458
30. Hart RG, Halperin JL (2001) Atrial
fibrillation and stroke: concepts and
controversies. Stroke 32:803–808
31. Timsit SG, Sacco RL, Mohr JP, Foulkes
MA, Tatemichi TK, Wolf PA, Price TR,
Hier DB (1993) Brain infarction severity differs according to cardiac or
arterial embolic source. Neurology
43:728–733