(Stroke. 2000;31:631.)
© 2000 American Heart Association, Inc.
Original Contributions |
Internal Borderzone Infarction
A Marker for Severe Stenosis in Patients With Symptomatic Internal Carotid Artery Disease
From the Department of Neuroscience and Neurorehabilitation, University of Genova, Genova, Italy (M.D.S.); The John P. Robarts Research Institute (M.E., V.C.H., H.J.M.B.) and the Departments of Clinical Neurological Sciences (M.E., V.C.H., A.J.F., H.J.M.B.) and Diagnostic Radiology (A.J.F.), University of Western Ontario, London, Ontario, Canada and the Neurology Unit, Rabin Medical Center, Campus Golda, Petach Tikva, and the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel (J.Y.S.).
Correspondence to H.J.M. Barnett, MD, The John P. Robarts Research Institute,100 Perth Drive, PO Box 5015, London, Ontario N6A 5K8, Canada.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose—Among subcortical infarctions, internal borderzone infarcts (IBI) are considered to be separate entities from perforating artery infarcts (PAI). The purpose of the present study is to examine the relationship between the presence of IBI and the degree of angiographically defined internal carotid artery (ICA) stenosis in symptomatic patients.
Methods—A review of 1253 brain CTs from patients recruited by the North American Symptomatic Carotid Endarterectomy Trial was performed, using templates for the identification of subcortical and cortical vascular territories.
Results—A total of 413 patients had visible ischemic lesions on the side ipsilateral to their symptomatic ICA. Of these, 138 had PAI, 108 had IBI, 122 had cortical infarcts, and 45 had a combination of different lesions. Mean (±SD) lesion diameter was larger for IBI (11.0±5.9 mm) than for PAI (7.1±4.7 mm) (P<0.001 for comparing 2 means). IBI was associated with higher degrees of ICA stenosis (P<0.001). Sixty-three percent of the patients with IBI had severe (70% to 99%) ICA stenosis compared with 42% of patients with PAI; 18% of the IBI patients had stenosis of 90% or more compared with 8% of the patients with PAI. Multiple logistic regression did not identify any patient characteristics as confounders.
Conclusions—Among subcortical infarctions, IBI are associated with higher degrees of ICA stenosis in symptomatic patients. Differentiating between internal borderzone and perforating artery infarcts is important, because each may arise from different mechanisms, namely, carotid disease and small-vessel disease, respectively.
Key Words: carotid stenosis • subcortical infarction • tomography, x-ray computed
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Arecently proposed classification system for subcortical infarctions, based on arterial territory, suggests that cerebral infarctions in the territory of deep and superficial perforating arteries be differentiated from infarctions in the vascular borderzone, located between the deep and superficial perforators.1 The borderzone type of subcortical infarct is referred to in the literature as an "internal borderzone infarct" or a "subcortical junctional infarct."1 2 A few studies comparing patients with internal borderzone infarction to patients with other types of cerebral infarction observed that patients with internal borderzone infarcts had a higher frequency of severe carotid stenosis and occlusion,3 diabetes mellitus,3 and heart disease.3 4 Other studies, taking into account the variability among vascular supply areas, did not confirm the association between internal borderzone infarction and severe carotid stenosis or occlusion4 5 but found a new association between chronic obstructive pulmonary disease combined with diabetes mellitus.4
The aim of the present study was to evaluate the characteristics of subcortical infarctions, identified by CT scans, in patients with ischemic symptoms and angiographically defined internal carotid artery (ICA) stenosis.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Subjects
Brain CT scans from 1253 patients, who were recruited between January 1, 1988, and August 16, 1991, into the North American Symptomatic Carotid Endarterectomy Trial (NASCET), formed the basis of the present study. Baseline characteristics of the patients have been described elsewhere.6 In brief, patients were entered into the trial if they were younger than 80 years, had transient ischemic attacks or nondisabling strokes in the carotid vascular territory within 120 days prior to randomization, and the participating center considered the degree of ICA stenosis to be 30% to 99% by angiography. Patients with ipsilateral internal carotid occlusion were not entered into the trial, nor were those with a possible cardiac source of emboli or with angiographic evidence of severe intracranial vascular disease.
Neuroimaging
Hard copies of all brain CT scans and angiographic images were
sent by the participating centers to the Central Office and were
reviewed initially by the trial’s principal neuroradiologist (A.J.F.).
In the majority of cases, CT scans were performed with a
third-generation scanner and with a distance of 10 mm between 2
slices. Biplane (anterior-posterior, lateral, and/or oblique) selective
carotid angiography was used for the assessment of the degree of
stenosis, using strict criteria. The degree of luminal linear
carotid stenosis was derived as a ratio, gauging the diameter
of the narrowest lumen as the numerator against the diameter of the
normal artery well beyond the carotid bulb and disease distally as the
denominator. Detailed examination of the state of the circle of Willis
was not feasible from the NASCET database.
All brain CT scans were subsequently reread by one of the authors
(M.D.S.), who was unaware of the clinical features and angiographic
results, with templates (Figure 1
) for
the identification of vascular territories.2 7 8 9 10 11 The
primary interest was in identifying all subcortical lesions and then
classifying them into different vascular territories and borderzone
areas. For each lesion identified, the mean of 2 measured perpendicular
diameters was calculated.
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Definitions
The CT lesions were classified into 3 categories: perforating
artery infarcts (PAI), internal borderzone infarcts (IBI), and cortical
infarcts (either territorial or watershed). PAI were identified,
according to the criteria of Ghika et al8 and
Bogousslavsky and Regli,2 as a hypodense area within the
vascular territory of deep perforators (region of the basal ganglia,
internal capsule, and thalamus) or superficial perforators (region of
the centrum ovale and external capsule). Infarcts in the territory of
the superficial perforators have been designated "white matter
medullary infarcts."10 IBI were defined as a hypodense
area in the vascular internal borderzone, where the border between the
deep and superficial perforating arteries divide the infarct into 2
approximately equal sections.1 2 3 9 11 12 13 Examples of IBI
are shown in Figures 2 and 3. Lesions more likely to be
leukoaraiosis14 were excluded. Cortical territorial
infarctions were defined as hypodense areas in the superficial vascular
territory of a main cerebral artery. Cortical watershed infarctions
were defined as hypodense areas in which the border between 2 main
cerebral arteries divided the infarct into 2 approximately equal
parts.8 13
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Statistical Analysis
The 
2 test and t test were
used to compare the lesion types with respect to patient
characteristics when the variables were categorical and continuous,
respectively. Multiple logistic regression analysis was used to
assess the association between degree of ICA stenosis and type
of lesion, while controlling for all patient characteristics.
Sixty-seven CT scans were reread blindly by one of the authors
(M.D.S.), and the reliability of being able to distinguish among no
lesion, PAI, IBI, and cortical lesions was high (
=0.94). The
reliability with which the reader was able to measure the dimension of
the lesion was also high (=0.85).
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Of the 1253 CT scans, 723 were bilaterally normal. Another 117 were normal, ipsilateral to the symptomatic carotid artery, but showed lesions on the contralateral side. Among the remaining patients with ipsilateral ischemic lesions, 138 had PAI, 108 had IBI, and 122 had cortical infarcts. There were 45 patients with a combination of different lesions. Because the primary interest was in comparing groups with single-type subcortical infarctions, the subsequent analyses were restricted to the 138 patients who had 162 PAI and the 108 who had 145 IBI. Eighty-three patients had only 1 IBI, 15 had 2 IBI, 8 had 3 IBI, and 2 had 4 IBI in the same hemisphere. All the patients with multiple lesions of the same type were counted only once in the analyses.
The patient characteristics in the 2 groups are shown in Table 1. Except for the degree of
ipsilateral ICA stenosis, no statistically significant
differences were observed between patients with PAI and IBI lesions,
although the presence of contralateral ICA occlusion was slightly
higher in the IBI group. The relationship between the degree of
stenosis and type of subcortical lesion is detailed in Figure 4. Sixty-three (45+18) percent of the
patients with IBI had severe (70% to 99%) carotid stenosis
compared with 42% (34+8) of patients with PAI (OR 2.3); 18% of the
IBI patients had stenosis of 90% or more compared with 8% of
the patients with PAI (OR 2.5). Results from the multiple logistic
regression analysis indicated that none of the patient
characteristics were confounding factors, and therefore the degree of
stenosis remained significantly different between the 2
groups.
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The distribution of the lesions in the different vascular territories
is shown in Table 2. The majority of the
PAI were located in the middle cerebral artery territory. Comparing the
diameter of the lesions shows that IBI are on average 3.9 mm
larger than PAI (P<0.001 for comparing 2 means). In fact,
more than twice as many (59.3% versus 23.5%) of the IBI were 10
mm or greater in comparison with the PAI.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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This is a large study on symptomatic patients with varying degrees of angiographically defined carotid artery stenosis and subcortical infarctions. Among all subcortical lesions seen on brain CT scans, IBI are associated with higher degrees of carotid stenosis. Patients with IBI are 2.3 times more likely to have severe (70% to 99%) ICA stenosis than patients with PAI.
The present study shows that internal borderzone infarcts are
larger than infarctions in the areas of perforating arteries, yet about
80% of them are smaller than 15 mm (Table 2b). Even if the
territory supplied by perforators may vary widely in different
subjects,8 9 11 the templates used in this study may be
useful in differentiating IBI from PAI (Figure 1
). Infarcts
within the vascular territory of perforating arteries are usually
smaller than IBI.7 15 In some cases of centrum ovale
infarction, it may be difficult to recognize IBI from infarction of the
superficial territory of middle cerebral,2 because of
anatomic variation. The presence of 2 or more lesions, appearing as a
chain of round infarcts along the internal vascular borderzone, can be
helpful in some cases (Figure 3). Several authors have
previously reported patients with carotid stenosis and
subcortical infarctions, although most of the lesions were
PAI.15 16 17 18 19 20 21
Lesions in the internal borderzone are attributed to the effects of severe stenosis and occlusion of the internal carotid or middle cerebral artery. Read et al10 reported a higher proportion of carotid stenosis or occlusion in 18 IBI compared with 22 white matter medullary infarcts (PAI in the territory of the superficial perforators). Angeloni et al12 performed angiography in 36 patients within 6 hours of an acute embolic stroke and reported 7 cases of internal borderzone infarctions and acute middle cerebral artery occlusion. Bogousslavsky and Regli13 reported 26 cases of internal carotid occlusion with "watershed infarctions," 6 of which were in the internal borderzone. In a CT-angiographic study, Wodarz22 found watershed infarctions (either cortical or in the internal borderzone) in 40% of 55 patients with carotid stenosis or occlusion. In a study of 107 patients with internal carotid occlusion, Ringelstein et al23 reported that 8 had watershed cortical infarctions and 36 had "subcortical terminal supply area infarctions." Waterston et al24 reported 10 cases of "small deep infarcts" associated with severe carotid stenosis or occlusion, and most of the small lesions were located in the internal borderzone areas. In a study of 383 patients with cerebral infarction, Gandolfo et al25 reported a significant role of carotid stenosis or occlusion in the formation of "pure" IBI. A recent study of 384 patients in the European Carotid Surgery Trial reported a tendency for borderzone infarction to occur more often distal to severe carotid disease, but the finding was not statistically significant.5
Previous reports have described IBI as the effect of hemodynamic impairment, due to severe carotid stenosis or occlusion, or to severe heart disease.3 4 26 27 The "hemodynamic theory" of IBI etiology is indirectly supported by some PET studies, which report a functional reduction of rCBF in the cortical watershed areas of patients with severe carotid disease.28 29 A recent study performed with SPECT showed a significantly lower perfusion reserve in patients with deep watershed infarction.30 Nevertheless, other functional studies have not confirmed these findings,31 32 and other clinical and experimental studies appear to support an embolic mechanism for both superficial territorial and watershed or internal borderzone infarctions.12 33 34 35 36 37 The perforating medullary arteries originating from the pial branches and reaching the deep white matter of the cerebral hemispheres are end arteries, as are the deep perforators.2 38 A partial or transient embolic occlusion of one main cerebral artery (or branches) may allow adequate flow in the lenticulostriate arteries, and sufficient collateral flow from the anastomotic network may restrict the area of infarction to the "last field," which in the case of IBI is the border between the deep and superficial perforators. The end result might be the formation of IBI.12 36 37
In conclusion, the present study, using a large sample size, demonstrates that for symptomatic patients with ICA disease and without severe cardiac disease, the presence of IBI is a marker for severe ICA stenosis. Therefore, IBI can be regarded as a separate entity from PAI, because of the higher likelihood of finding severe ICA stenosis in the presence of IBI.
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Acknowledgments |
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This study was supported by grant RO1-NS-24456 from the National Institute of Neurological Disorders and Stroke. The authors acknowledge the support of all participants in NASCET, and to SmithKline Beecham for providing Ecotrin for all NASCET patients. The authors would also like to thank Prof Domenico Inzitari for his helpful comments.
Received April 29, 1999; revision received December 28, 1999; accepted December 28, 1999.
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