Background and Purpose The compromise of cerebrovascular autoregulation in severe occlusive carotid artery disease depends on the functional capacity of collateral pathways. In previous reports correlating hemodynamic disturbances with collateral pathways, collateral blood supply was often evaluated by invasive cerebral angiography. In this study noninvasive transcranial Doppler ultrasound was used to determine both collateral pathways and vasomotor reactivity.
Methods With the use of blood flow direction, compression tests, and evident side-to-side asymmetries of blood velocities, the collateral supply through the anterior and posterior communicating arteries, the ophthalmic artery, and leptomeningeal anastomoses was evaluated by transcranial Doppler ultrasound in 48 patients (42 men, 6 women; mean±SD age, 59±9 years) with occlusion (n=36) or stenosis of more than 90% (n=12) of one internal carotid artery. Ipsilateral vasomotor reactivity was determined by the percent increase of middle cerebral artery mean blood velocity with the use of (1) the breath-holding maneuver and (2) acetazolamide (1 g IV) as vasodilatory stimulus. Additional stenoses (50% to <90%) of the contralateral internal carotid artery were present in 20 of the 48 patients.
Results Vasomotor reactivity was not affected by the presence of a contralateral internal carotid artery stenosis. Both vasodilatory stimuli similarly indicated poor vasomotor reactivity when an ophthalmic or a leptomeningeal pathway accompanied an anterior communicating artery pathway compared with a lone anterior communicating artery pathway (P<.05). The acetazolamide challenge indicated significantly better preserved vasomotor reactivity when blood supply was provided through a lone anterior communicating artery pathway (66±30%) than through an anterior and posterior communicating artery pathway (33±20%, P<.05), whereas the breath-holding method failed to show such a difference.
Conclusions The presence of an ophthalmic artery pathway may provide the first evidence of disturbed vasomotor reactivity. The use of cerebral angiography to evaluate collateral pathways must be considered carefully since transcranial Doppler ultrasound is a reliable noninvasive alternative.
In patients with occlusion or stenosis of more than 90% of the ICA, diminished VMR as a close correlate of cerebral autoregulatory capacity was reported to be significantly associated with low-flow infarctions1 2 3 4 and with a higher rate of future ipsilateral stroke compared with patients with a normal or only slightly disturbed VMR distal to such ICA lesions.5 6 The evaluation of rCBF by positron emission tomography,7 8 9 10 11 single-photon emission (clearance) techniques,3 12 13 14 or stable enhanced xenon CT15 demonstrated clearly that disturbances of cerebral autoregulatory capacity depend on the functional capacity of the collateral blood supply, thus favoring the opinion that the hemodynamic effect of severe ICA obstructions has previously been overestimated. In the aforementioned rCBF studies, the collateral pathways were classified into the willisian type (filling of the relevant MCA via the ACoA and/or the PCoA), in which the cerebral autoregulatory response was usually well preserved, and the ophthalmic (collateral blood flow mostly through the OA) and leptomeningeal types, in which autoregulatory capacity is severely decreased or diminished.
Cerebral angiography, which was predominantly used in the cited studies to determine the collateral pathways, is risky in patients with cerebrovascular diseases.16 17 18 19 TCD has been proven to accurately determine intracranial collateral pathways compared with cerebral angiography,20 and its measurement of blood velocity changes stimulated by acetazolamide or carbon dioxide correlates well with rCBF changes, indicating that VMR evaluated by blood velocity changes adequately reflects cerebral autoregulatory response.21 22 23 24 In one recent TCD study,4 the carbon dioxide–induced VMR was preserved when the collateral pathway evaluated exclusively by TCD was of the willisian type and was disturbed when blood supply was provided through a lone ophthalmic pathway. Because this study may have consequences for the diagnostic management of patients with severe occlusive carotid artery disease, eg, the angiographic evaluation of the collateral pathways, further confirmation is needed.
Subjects and Methods
Of the patients referred to our neurovascular laboratory for carotid artery examination by ultrasound, we selected 48 consecutive patients (42 men, 6 women; mean±SD age, 59±9 years; range, 25 to 81 years) who fulfilled three criteria: (1) angiographically proven occlusion or stenosis of more than 90% of only one ICA to allow for the assumption of a patent ACoA collateral pathway. Patients with an additional occlusion or stenosis of more than 90% of the contralateral ICA suggested either by angiography or by continuous-wave Doppler ultrasound were not included in the study; (2) technically adequate bilateral TCD examinations for determination of collateral pathways; and (3) no evidence of an additional stenosis of an intracranial artery by TCD or by angiography in which the intracranial arteries were visualized.
All patients received a continuous-wave Doppler ultrasound examination (SPEAD 6, Spead Electronique; 4-MHz probe) to classify the findings of the contralateral ICA with use of published criteria.25 Briefly, a stenosis of 50% to 70% was diagnosed when a blood velocity increase at the ICA origin was accompanied by a turbulent murmur strongly limited to the poststenotic ICA. A stenosis of more than 70% to less than 90% was indicated by a severe blood velocity increase at the ICA origin and a continuing turbulent murmur to the distal submandibular ICA; the blood flow direction in the supraorbital artery remained orthograde. A stenosis of 90% or more was diagnosed when in addition the blood flow in the submandibular ICA was severely reduced or the blood flow direction in the supraorbital artery was reversed. The vertebral arteries were also insonated by continuous-wave Doppler at the atlantal slope and at their origins, but the vertebral artery findings were not taken into consideration for this study. All patients had received a cranial CT before cerebral angiography.
The TCD examinations (TC 2-64, EME; 2-MHz pulsed hand-held probe) were performed while the patients were in a supine position and included the bilateral transtemporal insonation of the MCA (at a depth of 50 to 55 mm), the ACA (at a depth of 60 to 70 mm), and the P1- and the P2-segment of the PCA (at a depth of 55 to 65 mm). The basilar artery was insonated at a depth of 85 mm or more through the transnuchal approach while the patients remained in the lying supine position with the head turned slightly away from the ICA in cases of occlusion or stenosis of 90% or more; additionally, the head was positioned slightly forward with the help of a small pillow. The site of compression of the contralateral common carotid artery was allocated as proximal as possible. For the measurement of blood velocity, the most powerful signal at the highest mean blood velocity level that was recorded constantly during a 10-second period was used. For technical details and for a discussion of the accuracy of TCD in identifying intracranial collateral pathways, see previous reports.20 26 Briefly, the following criteria were used to classify the pathways: a patent ACoA was indicated by a reversed blood flow in the A1 segment of the ACA ipsilateral to the relevant MCA or by a prompt fall of blood velocity in the relevant MCA after compression of the nonoccluded contralateral common carotid artery. A patent PCoA was indicated by a marked increase of blood velocity in the basilar artery or in the P1 segment of the PCA ipsilateral to the relevant ICA after compression of the nonoccluded contralateral common carotid artery.
The mean blood velocity reference values for our laboratory are 40±6 cm/s (range, 24 to 50 cm/s) for the PCA and 46±10 cm/s (range, 20 to 72 cm/s) for the ACA.20 An LM was indicated by evident side-to-side asymmetry of mean blood velocity in the proximal ACA in the condition of an orthograde blood flow direction in both ACAs or in the P2 segment of the PCA, with a high blood velocity exceeding the upper limit of the normal blood velocity range ipsilateral to the relevant ICA. For example, when the mean blood velocity in the P2 segment of the PCA ipsilateral to the relevant MCA was 60 cm/s and in the contralateral P2 segment 43 cm/s, we classified such a finding in the ipsilateral P2 segment of the PCA as LM. By the ophthalmic approach, the OA was insonated at a depth of 45 to 50 mm to determine blood flow direction.
The collateral blood supply for each MCA investigated was classified as follows: lone ACoA (n=8), ACoA/OA (n=10), ACoA/PCoA (n=14), ACoA/PCoA/OA (n=5), PCoA/OA (n=5), and LM (n=6). All patients of the LM group exhibited collateral supply through both the circle of Willis and the OA.
Assessment of VMR
VMR was assessed only ipsilateral to the ICA with occlusion or stenosis of more than 90%. The VMR on the contralateral side was not evaluated. The assessment of VMR was performed with the use of two different vasodilatory stimuli: (1) carbon dioxide by means of breath-holding and (2) acetazolamide, which is a potent vasodilator of cerebral resistance vessels, leading to a smooth increase of blood velocity with plateauing of blood velocity after 10 to 15 minutes.27 28
The breath-holding test was performed according to the procedure of Markus and Harrison.29 After normal breathing of room air for approximately 4 minutes, the patients were instructed to hold their breath after a normal inspiration. During the maneuver, the MCA mean blood velocity was recorded continuously. The mean blood velocity at the TCD display immediately after the end of the breath-holding period was recorded as the maximal increase of the MCA mean blood velocity (during breath-holding). The time of breath-holding was also recorded. This procedure was repeated after a rest of 2 to 3 minutes to allow mean blood velocities to return to their initial values. For the maximal MCA mean blood velocity increase and for the time of breath-holding, the mean values of both trials were used. BHI was calculated as percent increase in MCA mean blood velocity recorded during breath-holding divided by the seconds of breath-holding, or (Vbh−Vr/Vr) · 100 · s−1, where Vbh is MCA mean blood velocity at the end of the breath-holding, Vr the MCA mean blood velocity at rest, and s−1 per second of breath-holding.
The acetazolamide test was performed after a break of 5 minutes. After the resting value was recorded, acetazolamide stimulation was induced by administration of 1 g acetazolamide IV over 5 minutes. Fifteen minutes after the application of acetazolamide, the mean blood velocities were measured again with the ultrasound sample volume in the same depth of the MCA compared with the resting examination, again measuring the highest mean blood velocity that could have been recorded constantly over a period of 10 seconds. The %VMRacet was calculated as percent change in MCA mean blood velocity after stimulus application compared with mean blood velocity at rest, or (Vacet−Vr/Vr) · 100, where Vacet is the maximal increase of the MCA mean blood velocity after acetazolamide application and Vr the mean blood velocity at rest.
All values are given as mean±SD. The analysis was performed with the Spss/pc+ statistical package. With the use of the Kolmogorov-Smirnov test for comparison with a normal distribution, the values of %VMRacet and BHI did not differ from a normal distribution. The ability of %VMRacet and BHI to differentiate between the groups of collateral supply was analyzed by one-way ANOVA for multiple comparisons (Duncan’s test; a value of P=.05 was considered significant). The ANOVA procedure was used to analyze whether VMR was affected by the presence of a contralateral ICA stenosis and by the clinical symptoms.
Thirty-six of the 48 patients exhibited an occlusion of the relevant ICA, 12 a stenosis of more than 90%. The contralateral ICA was normal in 28 patients and exhibited an asymptomatic stenosis between 50% and less than 90% in 20 patients. Stenoses of the contralateral ICA were found in 3 of the 8 patients with an ACoA pathway (all three stenoses between 50% and 70%), 4 of the 10 patients with an ACoA/OA pathway (two 50% to 70%, two >70% to <90%), 5 of the 14 patients with an ACoA/PCoA pathway (four 50% to 70%, one >70% to <90%), 2 of the 5 patients with an ACoA/PCoA/OA pathway (both >70% to <90%), 4 of the 6 patients with LM pathways (two 50% to 70%, two >70% to <90%), and 2 of the 5 patients with a PCoA/OA pathway (both >70% to <90%).
Twenty-two patients were asymptomatic, and 26 suffered from symptoms ipsilateral to the relevant ICA within 3 months before the actual investigation (minor stroke in 13, major stroke in 6, transient ischemic attack in 3, a branch retinal artery occlusion in 2, prolonged reversible ischemic neurological deficit in 1, and amaurosis fugax attack in 1). The findings of the contralateral ICA (with stenosis: %VMRacet, 24±20%; BHI, 0.53±0.38%/s; without stenosis: %VMRacet, 35±24%; BHI, 0.70±0.36%/s) as well as the clinical presentation (symptomatic: %VMRacet, 28±22%; BHI, 0.57±0.37%/s; asymptomatic: %VMRacet, 34±24%; BHI, 0.70±0.37%/s) did not affect the %VMRacet or the BHI significantly.
The %VMRacet differentiated significantly between the different groups of collateral pathways (Table⇓). The %VMRacet was best preserved in patients with a lone ACoA collateral pathway. Compared with this pathway, all other types of collateral supply showed a significantly reduced %VMRacet (Table⇓). %VMRacet was significantly lower in the ACoA/PCoA/OA group compared with the ACoA/PCoA group. It was also significantly different when the ACoA/PCoA and the PCoA/OA types of collateralization were compared with the LM group, in which %VMRacet was poorest.
The BHI was not significantly different between the collateral pathway groups of lone ACoA, ACoA/PCoA, and PCoA/OA. Compared with the lone ACoA group, the BHI was significantly reduced in the groups of ACoA/OA, ACoA/PCoA/OA, and LM (Table⇑).
TCD is a well-established tool for evaluating intracranial collateral pathways.4 20 26 In regard to the use of compression tests to identify collateral channels, one has to consider that collateral pathways detected by compression tests are only pathways that may be recruited when needed and therefore may not contribute to the demanded blood supply at the time of their actual evaluation. In a previous study in which TCD was compared with cerebral angiography20 to evaluate collateral pathways, we found that an actual patent ACoA or PCoA pathway demonstrated by angiography was sometimes detected by TCD only by use of compression tests while the mean blood velocity was within the normal range. Mean blood velocity within the normal range did not distinguish between pathways with and without an actual contribution to the collateral supply. Therefore, it seems that compression tests accentuate used collateral pathways.
The anatomic variability of the circle of Willis has to be considered for interpretation of our results. In all groups with an OA pathway present, VMR was significantly reduced except for the PCoA/OA group. VMR in the PCoA/OA group was similar to the VMR of the ACoA/PCoA and the lone ACoA groups (with respect to BHI), assuming full functional capacity of the PCoA pathway while the ACoA was absent. Therefore, one has to consider whether the OA in the PCoA/OA group really does contribute to the blood supply of the ipsilateral MCA.30
We used two different methods of VMR testing. The breath-holding method as a carbon dioxide–dependent VMR test is comparable to VMR tests that use the full range of mean blood velocity reactivity at hypercapnia and hypocapnia to a highly significant degree.29 Using the full range of blood velocity reactivity during hypercapnia and hypocapnia for VMR evaluation, Ringelstein et al4 found a well-preserved VMR when collateral supply was provided through a patent ACoA, PCoA, or ACoA/PCoA irrespective of the blood flow direction in the OA; they found a significantly decreased VMR when collateral supply was provided through the OA only. Because of the different classification of the groups of collateral pathways, our results cannot be compared directly with theirs. As long as an OA pathway was absent in our patients, VMR with respect to the BHI was good and was not different between the ACoA and ACoA/PCoA groups, which is in accordance with the results of Ringelstein et al. However, contrary to their findings we found a decreased VMR in most of the patients with a blood supply through the circle of Willis when accompanied by an OA pathway. In previous rCBF studies,8 12 15 the autoregulatory capacity ipsilateral to an ICA occlusion was decreased at least only slightly when the collateralization was provided through the circle of Willis accompanied by an OA pathway. These results are more in accord with those of Ringelstein et al.4 That we found a significant VMR decrease in the presence of an OA pathway may be due to the inhomogeneity of our total group of patients. One fourth of the relevant ICAs exhibited a stenosis of more than 90%, a condition in which VMR can be decreased to a greater extent than in ICA occlusion.24 Additionally, the hemodynamic effects of the contralateral ICA stenoses have to be considered. A decreased VMR ipsilateral to an ICA occlusion has been reported to be associated with a stenosis of more than 50% of the contralateral ICA.12 31 Although not significant in our patients, VMR ipsilateral to the investigated ICA was lower in the instances with a contralateral ICA stenosis than in those without a contralateral stenosis. Such hemodynamic considerations may partly explain that the collateral supply through the circle of Willis was impaired in the ACoA/OA, ACoA/PCoA/OA, and LM groups. Particularly in our LM group, four of the six patients exhibited an additional contralateral ICA stenosis of 50% or more.
The acetazolamide test was additionally performed by us because the acetazolamide challenge has been reported to differentiate more accurately between various subgroups of patients with occlusive carotid artery disease.24 31 By means of the BHI the collateral supply was similarly adequate in the lone ACoA, ACoA/PCoA, and PCoA/OA groups. Our %VMRacet findings, however, indicate a most dominant position of the ACoA pathway within these three groups.
To summarize, our study demonstrates the ability of TCD to conclusively evaluate the relationship between VMR and the collateral pathways, including the concept of their stepwise recruitment. When the circle of Willis is not sufficient, the OA pathway seems the first to be recruited. The presence of leptomeningeal pathways indicates the most compromised collateral supply. Cerebral angiography is risky and should be considered carefully when collateral pathways are to be examined. However, TCD investigations rely strongly on the experience of the examiner.
Selected Abbreviations and Acronyms
|ACA||=||anterior cerebral artery|
|ACoA||=||anterior communicating artery|
|BHI||=||breath-holding index in percent mean blood velocity increase per second of breath-holding|
|ICA||=||internal carotid artery|
|MCA||=||middle cerebral artery|
|PCA||=||posterior cerebral artery|
|PCoA||=||posterior communicating artery|
|TCD||=||transcranial Doppler ultrasonography|
|%VMRacet||=||vasomotor reactivity in percent mean blood velocity increase after 1 g acetazolamide IV|
- Received March 7, 1995.
- Revision received June 15, 1995.
- Accepted November 7, 1995.
- Copyright © 1996 by American Heart Association
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