(Stroke. 1999;30:593-598.)
© 1999 American Heart Association, Inc.
Original Contributions |
Outcome of Carotid Artery Occlusion Is Predicted by Cerebrovascular Reactivity
From the AFaR CRCCS: Divisione di Neurologia-Ospedale Fatebenefratelli, Isola Tiberina, Roma (F.V., P.P., F.P., P.M.R.); IRCCS "Centro S.Giovanni di Dio" FBF, Brescia (P.M.R.); and Clinica Neurologica, Università di Roma "Tor Vergata and IRCCS "S. Lucia," Roma (M.S.).
Correspondence to Dr Mauro Silvestrini, Clinica Neurologica, Università di Roma "Tor Vergata," Ospedale S.Eugenio, P.le dell'Umanesimo 10, 00144 Roma, Italy. E-mail fbfisola{at}tin.it
 |
Abstract |
|---|
 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
Background and Purpose—The purpose of this study was to investigate the possibility of obtaining prognostic indications in patients with internal carotid occlusion on the basis of intracranial hemodynamic status, presence of previous symptoms of cerebrovascular failure, and baseline characteristics.
Methods—Cerebral hemodynamics were studied with transcranial Doppler ultrasonography. Cerebrovascular reactivity to apnea was calculated by means of the breath-holding index (BHI) in the middle cerebral arteries. Sixty-five patients with internal carotid artery occlusion were followed-up prospectively (median, 24 months), 23 patients were asymptomatic and 42 symptomatic (20 with transient ischemic attack and 22 with stroke).
Results—During the follow-up period, 11 symptomatic patients and 1 asymptomatic patient had another ischemic event ipsilateral to carotid occlusion. Among factors considered, only lower BHI values in the middle cerebral arteries ipsilateral to carotid occlusion and older age were significantly associated with the risk of developing symptoms (P=0.002 and P=0.003, respectively; Cox regression multivariate analysis). Based on our data, a cut point of the BHI value for distinguishing between pathological and normal cerebrovascular reactivity was determined to be 0.69. All patients except one, who developed TIA or stroke during the follow-up period, had BHI values ipsilateral to carotid occlusion of <0.69.
Conclusions—These data suggest that impaired cerebrovascular reactivity is predictive for cerebral ischemic events in patients with carotid occlusion.
Key Words: carotid occlusion • cerebrovascular circulation • stroke • ultrasonography, Doppler, transcranial
|
Introduction |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The outcome of internal carotid artery (ICA) occlusion is highly variable. Klijn et al1 reviewed 20 observational studies published between 1960 and 1995 that investigated the risk of stroke in patients with occlusion of the ICA. The annual stroke rate varied between 0% and 20%. In these studies, measurements of the cerebral blood flow (CBF) were not performed. Several follow-up studies have attempted to show a correlation between an increased risk of stroke ipsilateral to an occluded internal carotid artery and a compromised CBF; assessments were made with the use of various methods.2 3 4 5 6 7 8 The results have not been unequivocal. Moreover, other studies have demonstrated a lower annual stroke risk in asymptomatic patients with ICA occlusion than in symptomatic patients.9 10 Recently, Derdeyn et al11 demonstrated that compromised CBF in patients with ICA occlusion is associated with the presence of previous ischemic symptoms and with no other risk factors; consequently, they remarked on the importance of distinguishing between symptomatic and asymptomatic patients in further investigations of the relationship between hemodynamic compromise and stroke risk.
Transcranial Doppler (TCD) ultrasonography is a noninvasive and nonradioactive technique for evaluation of the blood flow velocity in large cerebral vessels.12 13 14 Compared with other available methods of CBF investigation such as positron emission tomography (PET) and single-photon emission CT, TCD ultrasonography is much less expensive, simpler, and faster. TCD ultrasonography has been used to measure cerebral perfusion or cerebrovascular reactivity (CVR) because normal cerebral artery blood flow velocity increases in response to a vasodilatatory stimulus such as hypercapnia, which is usually induced by CO2 inhalation or acetazolamide administration.15 16 A decreased CVR indicates the presence of preexisting vasodilatation, which reflects a reduced reserve capacity of cerebral autoregulation.
The purpose of this study was to evaluate the possibility of obtaining prognostic indications by means of a simple and noninvasive method of induction of hypercapnia. For this purpose, we used a fixed period of apnea and calculated CVR by means of the breath-holding index (BHI) and evaluated its predictivity for cerebral ischemic events in patients with symptomatic and asymptomatic carotid artery occlusion. The possible role of baseline clinical and epidemiological characteristics in influencing the prognosis of such patients was also considered.
|
Subjects and Methods |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The participants in the study were recruited from consecutive patients with occlusion of the extracranial segment of the internal carotid artery admitted to our stroke unit from April 1993 to May 1997 for a transient ischemic attack (TIA) involving the vascular territory of middle cerebral artery (MCA) or for a functionally independent or minor stroke (Rankin Scale score of 1 to 2) in the same district. Patients with major stroke were not considered because of the difficulty of obtaining their full cooperation and of evaluating the occurrence of any further ischemic event. Exclusion criteria were poor insonation of the temporal bone window, possible or probable embolizing cardiopathy (atrial fibrillation, mitral valve stenosis, prolapse or calcification, mechanical cardiac valves, recent myocardial infarction, left ventricular thrombus, atrial myxoma, endocarditis, dilated cardiomyopathies, and patent foramen ovale), stenosis
30% in the carotid artery contralateral to the
occluded one, and significant alteration of the vertebral arteries. Of
the 47 recruited patients, 5 were excluded (3 for poor insonation of
the temporal bone window, and 2 for the presence of cardiopathies).
Among the 42 included patients, 20 had TIA and 22 had minor stroke.
Twenty-three patients with asymptomatic carotid occlusion
were also enrolled during the same period. These patients were selected
from 25 consecutive subjects who underwent ultrasonographic examination
in the outpatient department and who were referred by their general
practitioner for suspected carotid stenosis. Two
patients were excluded for a poor insonation of the temporal bone
window. All patients underwent a careful neurological and cardiological
examination, ECG, transthoracic or
transesophageal echocardiography,
and brain CT scan or MRI. Moreover, complete blood chemistries and a
clinical history with particular attention to the major vascular risk
factors (hypertension, diabetes, smoking, and
hyperlipidemia) were obtained from each patient.
Patients were reinvestigated clinically every 6 months; end points were
defined as ipsilateral TIA, stroke, or death. The severity of stroke
that occurred during the follow-up period was assessed by means of the
Rankin Scale (score 0 to 2: minor stroke; 3 to 5: major stroke). This
evaluation was performed at least 2 months after stroke. During the
study period, no patient underwent surgical intervention and no dropout
occurred. Carotid artery disease was assessed and defined by color flow B-mode Doppler ultrasound (SPR 8000 Esaote Biomedica, Italy) according to the standardized criteria.17 18 The vertebrobasilar system was evaluated as described by Bartels.19 Additional conventional angiography was performed in the 42 symptomatic patients and in 3 asymptomatic patients. In these patients, the degree of carotid stenosis contralateral to the occlusion was quantified according to the North American Symptomatic Carotid Endarterectomy Trial (NASCET) criteria.20
Intracranial vessels were examined by means of a Multi-Dop X/TCD transcranial Doppler instrument (DWL Elektronische Systeme GmbH). CVR to hypercapnia was evaluated by means of the BHI at the beginning of the observation period. The index is obtained by dividing the percent increase in mean flow velocity (MFV) occurring during breath-holding by the length of time (seconds) that subjects hold their breath after a normal inspiration [(MFV at the end of breath-holding – rest MFV/rest MFV)x100/second of breath-holding]. End-tidal expiratory CO2 was measured by means of a capnometer (Oxy-cap Datex). All subjects were normocapnic. The study was performed in a quiet room, with the subject lying in a comfortable supine position without visual or auditory stimulation. Evaluation of CVR was performed in the early morning by the same 2 operators, who were unaware of the patient's clinical status (except when signs of stroke were evident) and the results of the extracranial carotid studies. Two dual 2-MHZ transducers fitted on a headband and placed on the temporal bone windows were used to obtain a bilateral continuous measurement of MFV in the MCAs. MFV and end-tidal CO2 at rest were obtained by the continuous recording of a 2-minute period of normal room air breathing. During the same period, mean blood pressure and heart rate were continuously monitored by means of a blood pressure monitor (2300 Finapress, Ohmeda). After a breath-holding period, MFV, mean blood pressure, and heart rate over a 4-second interval were recorded. Subjects were asked to hold their breath for 30 seconds after a normal inspiration. The exact length of apnea was checked by means of the respiratory activity monitor. All the study subjects were able to hold their breath for the required period. End-tidal CO2 during the first exhalation after apnea was evaluated. Before proceeding to the definitive recording, patients were trained to perform the procedure correctly. BHI was calculated when the rise in end-tidal CO2 from baseline to the first expiration after breath-holding was >8 mm Hg. This method of induction of hypercapnia proved to be effective and reproducible in the study of cerebral hemodynamics in both normal and pathological conditions.21 22
Breath-holding indices were also measured in 30 subjects (17 men, 13 women; mean age, 62±5.5) recruited from consecutive patients with vascular risk factors who underwent ultrasonic examination, which excluded any vascular stenosis. This group allowed us to define normative ranges for BHI values and thus to recode cerebral hemodynamic parameters in our patients as either compromised or normal.
In symptomatic patients, all TCD ultrasonography evaluations were performed at least 3 months after stroke (range 92 to 105 days) because it has been demonstrated that cerebral hemodynamics may be disturbed during the first days after stroke.23 Moreover, it has been shown that CVR usually improves, probably because of the full development of intracranial collaterals, 2 to 3 months after the occlusion has occurred.24 25
Examination of vessels of the circle of Willis was performed as described by Aaslid et al.13 The patency of major collateral vessels, namely ophthalmic, anterior, and posterior communicating arteries, was evaluated by means of compression tests. Blood flow through these 3 major collateral vessels was determined as a residual flow in MCA after each compression.26 27 Moreover, collateralization was assumed through the anterior part of the circle of Willis when anterior cerebral artery flow ipsilateral to the carotid occlusion was reversed (this usually occurred in conjunction with acceleration of the contralateral anterior cerebral artery); through the external carotid artery when ophthalmic flow was reversed; and through the basilar artery when the ratio of ipsilateral to contralateral velocity in the posterior cerebral artery was >50%. All 3 possible collateral sources were assessed.28
The annual rate of adverse events was calculated by means of
person/year method. The Kaplan-Meier procedure was used to plot and
compare cumulative hazard of the considered groups, and Cox regression
analysis allowed us to determine the factors that could be
considered as independent predictors of ipsilateral ischemic
events. Relative risks (RRs) and 95% CIs were reported to indicate the
effect size. Spearman's 
coefficient was applied to verify
correlation between the examined variables. Normative ranges for
BHI (mean±2 SD) were calculated after logarithmic transformation of
raw data to better fit a normal distribution (Shapiro-Wilks statistic
was used to test normality). The analyses were performed with
the use of SPSS 7.0 software (SPSS Inc). The significance level was set
at 0.05 throughout the statistical analysis.
The study was approved by the local ethics committee, and each subject gave informed consent.
|
Results |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The median follow-up of the 65 patients was 24 months (minimum=8; maximum=61). Fifteen were women (23.1%), and 50 were men (76.9%). Mean(±SD) age was 67.8 years±5.5. Mean BHI value of symptomatic patients was significantly lower than that of asymptomatic ones (P<0.001). Only 1 of the 23 asymptomatic patients (4%) had an ipsilateral minor stroke after 33 months from the enrollment in this study, which resulted in an annual stroke rate of 1.6%. Four of 20 patients with TIA (20%) experienced an ipsilateral vascular event: 2 had a stroke (1 minor and 1 major stroke) and the remaining developed a TIA (annual ipsilateral ischemic event rate=9.0%; annual stroke rate=4.5%). In the group of 22 patients with nondisabling stroke, 7 patients experienced a vascular event (32%): 6 had a stroke (2 minor and 4 major strokes) and 1 had a TIA. This resulted in an annual ipsilateral ischemic event rate of 14.6% and an annual stroke rate of 12.5%. All ischemic events in the 2 symptomatic groups occurred between 8 and 25 months from the beginning of the study, with a global annual ipsilateral ischemic event rate of 11.9% (Figure 1
). During the follow-up period, only 3
cerebrovascular ischemic events occurred contralateral to
carotid occlusion (1 in the TIA group, and 2 in the stroke group). In
all cases, the strokes were minor.
|
,
asymptomatic (n=23); 
, TIA (n=20); 
, stroke (n=22);
and +, censored.
Patient characteristics are reported in Table 1. To determine the variables
(baseline risk factors, symptomaticity, and cerebral
hemodynamic parameters) that could predict
an ischemic event ipsilateral to the occluded artery, the Cox
proportional hazard regression model was applied; patients were
considered censored if no event or contralateral ischemic event
occurred. Both univariate and multivariate
procedures were used: the former to ascertain the role of variables
as alone; the latter to determine the factors that remain in the final
model as independent predictive factors. All results are reported in
Table 2. Only BHI, age, and the number of
collateral circles reached the stated significance level
(P=0.05) in the univariate analysis. In
the multivariate analysis, at the first step,
BHI entered the model, followed by age (second step), and no other
variables could be added to improve the model. In fact, the effect
of the number of collateral circles is reduced with respect to the
univariate approach, probably because of the significant
correlation with BHI (Spearman's =0.36; P=0.003).
Nevertheless, its RR is near significance, as shown in Table 2.
|
|
Because an inverse correlation is expected between BHI values and risk
of ischemic event occurrence (the lower the BHI, the higher the
risk), we preferred to change the sign of the BHI and to multiply the
original value by 10, to simplify the interpretation of the RR. In this
manner, by looking at the statistics reported in Table 2
, we can
observe that a BHI decrement of 0.10 induces an RR equal to 1.30, which
indicates that the risk of a stroke during the entire follow-up is
increased by 30%. In addition, the effect of age resulted in a RR of
1.23, meaning that for each year the risk tends to increase by
23%.
On the basis of data collected in control subjects, we tried to obtain
a cut point for the BHI value in which a subject should be considered
as having a pathological CVR. For this purpose, a logarithmic
transformation was applied to data to achieve a better fit to the
normal distribution (Shapiro-Wilks statistic=0.95; df=30;
P=0.21 [not significant]). Because >95% of cases would
fall within the interval (mean±2 SD with the assumption of normality),
the value mean-2 SD was chosen as threshold. This procedure provided a
cut point of 0.69 as the normative threshold value for BHI. All 30
control subjects, 20 asymptomatic patients, and 9
symptomatic patients (8 TIA and 1 stroke) had BHI values
above the normative threshold; 3 asymptomatic patients and
33 symptomatic patients (12 TIA and 21 stroke) were below
the defined cut point. By the replacement of the BHI as continuous
variable with the BHI as dichotomous factor (pathological: <0.69;
normal 0.69), the results of Cox regression were perfectly
consistent, which suggested only BHI and age as potential
predictive factors. In fact, 11 of 12 patients who developed symptoms
ipsilateral to the occlusion had BHI values <0.69. All of them had
experienced previous symptoms. The only asymptomatic
patient who had a stroke during follow-up also had a BHI above the
threshold value. The Kaplan-Meier representation of follow-up
in patients with and without pathological BHI values is plotted in
Figure 2.
|
, BHI<0.69;
Finally, predicted probability of ipsilateral ischemic events
was plotted against age and the 2 BHI groups (Figure 3). The effect of age emerges as more
important in patients with pathological BHI values and allows us to
identify a subgroup of patients at major risk of an adverse event.
|
|
Discussion |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
The results of our study show that an impairment of CVR to hypercapnia is significantly associated with an increased risk of ischemic events ipsilateral to carotid occlusion. In fact, in our study population, 11 of 12 patients who developed an ischemic event during the follow-up period had a BHI value <0.69. Four of these 11 patients were in the TIA group; the remaining 7 subjects had experienced a previous minor stroke. In all cases, neurological events occurred in the first 25 months of follow-up. On the other hand, only 1 of the 29 subjects with a BHI value >0.69 developed symptoms 33 months after entering the study. Moreover, this subject was the only asymptomatic patient who had a stroke during the follow-up period. On the basis of these data, low values of BHI can be considered the most important factor for predicting further cerebrovascular ischemic events in patients with ICA occlusion. Among the other factors considered, only age approached significant association with symptomaticity. As shown in Figure 3
, a clear interaction between BHI and age was found, which
suggested that the effect of age becomes important when combined with
an impaired CVR. On the other hand, the risk of a further cerebral
ischemic event, in normal cerebral
hemodynamics, does not appear to be strongly associated
to age. The RR of a lower number of collateral vessels was near
significance, and it could be interesting to develop this finding in an
additional investigation. The apparent contradiction of the lack of
correlation between low number of collaterals and reduced CVR could be
explained by postulating that BHI is a more accurate
hemodynamic measure than the evaluation of the number
of collaterals whose efficiency cannot be quantified by the simple
determination of their presence. There is much evidence to suggest that, in addition to embolism, compromised cerebral blood flow may play an important role in causing ipsilateral ischemic events in patients with occlusion of the ICA; in these cases, ischemia would occur by the failure of the collateral blood flow through the circle of Willis, the ophthalmic artery, or the leptomeningeal collaterals.1 29
To date, 7 follow-up studies have compared prognosis in medically treated patients with and without compromised cerebral blood flow, evaluated by different methods (PET, single-photon emission CT, xenon CT, and TCD). In 3 of the 7 studies,2 3 4 no clear association between a compromised CBF and an increased risk of stroke during follow-up could be demonstrated. On the contrary, in each of the other 4 studies,5 6 7 8 patients with compromised CBF were shown to have a worse prognosis than similar patients with normal CBF measurements. In particular, in 1 of these studies, Kleiser and Widder5 investigated CVR by means of a transcranial Doppler CO2 test in 85 patients with ICA occlusion. They distinguished between 3 categories of sufficient, diminished, and exhausted cerebrovascular capacity. A significant correlation between ipsilateral ischemic events and a diminished or exhausted CO2 reactivity was found. In cases with exhausted CVR, neurological events occurred more often during the first months.8 Note that in the study reported, the authors had not distinguished between symptomatic and asymptomatic patients, and the data were not analyzed separately for these 2 groups.
Recently, Derdeyn et al11 investigated the relationship between misery perfusion (increased oxygen extraction fraction, [OEF]) and risk factors in patients with carotid occlusion by PET. The data showed that the presence of increased OEF is associated with prior ischemic symptoms and not with the other considered risk factors for stroke. This finding is consistent with an association between prior ipsilateral symptoms and absent CO2 reactivity assessed by TCD.24 The fact that asymptomatic patients had lower frequency of hemodynamic abnormalities (increased OEF) must be taken into consideration when investigating the relationship between hemodynamic factors and stroke risk. This assumption is in accordance with our results. In fact, we found that symptomatic patients had significantly lower BHI values than asymptomatic ones. However, our results also suggest that the reduction of CVR to apnea is associated with an increased risk of further ischemic events and not only with a previous TIA or stroke.
The importance of hemodynamic factors in influencing the prognosis of patients with carotid occlusion is also suggested by the evidence that ICA occlusion is one of the main causes of border-zone infarction, and this association is more evident in the presence of compromised cerebral hemodynamics.30 In our study, we did not find a particularly high prevalence of watershed infarction. In fact, in the 9 strokes ipsilateral to carotid occlusion that occurred during follow-up period, CT or MRI examination showed watershed infarction in only 3 cases. This finding, however, does not play down the possible implications of hemodynamic factors in the pathogenesis of stroke associated with carotid occlusion. In fact, it has been demonstrated that the possibility of tissue damage due to a cerebral embolic event, which is still considered the main pathogenic mechanism of a cerebral ischemic event, is higher in the presence of an impaired capability of cerebral vessels to adapt their caliber after vasodilatatory stimulus.31
On the basis of these considerations, it has been suggested that the therapeutic approach selected for patients with carotid artery occlusion could be differentiated on the basis of cerebral hemodynamic status.1 The actual therapeutic options in patients with ICA occlusion seem to be limited after the failure of the extracranial/intracranial (EC/IC) bypass surgery.32 However, in the EC/IC bypass trials, selection of patients based on the CVR had not been performed in spite of the fact that this surgical approach has been associated with an improvement of cerebral hemodynamics.33 In this study, we have demonstrated that intracerebral hemodynamic consequences of carotid occlusion can be very different. Exhausted or diminished CVR and an established BHI value, determined in our data to be <0.69, could constitute the basis for reconsidering the possibility of testing the efficacy of the classic or a new type34 of surgical EC/IC bypass approach in a subgroup of patients considered to be at highest risk of developing stroke and with the most favorable odds of benefiting from surgical intervention. In this study, we considered patients with strictly unilateral internal carotid occlusion. The possible application of our results to other conditions such as bilateral carotid occlusion or carotid occlusion associated with contralateral hemodynamically significant stenosis should be validated by additional studies.
|
Acknowledgments |
|---|
This study was supported in part by the Italian Ministry of University and Scientific Research.
Received November 12, 1998; revision received December 22, 1998; accepted December 22, 1998.
|
References |
|---|
|
TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
|---|
1. Klijn CJM, Kappelle LJ, Tulleken CAF, van Gijn J. Symptomatic carotid artery occlusion: a reappraisal of hemodynamic factors. Stroke. 1997;28:2084–2093.
2. Powers WJ, Tempel LW, Grubb RL. Influence of cerebral hemodynamics on stroke risk: one year of follow-up of 30 medically treated patients. Ann Neurol. 1989;25:325–330.[Medline] [Order article via Infotrieve]
3. Hasegawa Y, Yamaguchi T, Tsuchiya T, Minematsu K, Nishimura T. Sequential change of hemodynamic reserve in patients with major cerebral artery occlusion or severe stenosis. Neuroradiology. 1992;34:15–21.[Medline] [Order article via Infotrieve]
4.
Yokota C, HasegawaY, Minematsu K, Yamaguchi T. Effect
of acetazolamide reactivity and long-term outcome in
patients with major cerebral artery occlusive diseases.
Stroke. 1998;29:640–644.
5.
Kleiser B, Widder B. Course of carotid artery
occlusion with impaired cerebrovascular reactivity. Stroke. 1992;23:171–174.
6. Yonas H, Smith HA, Durham SR, Pentheny SL, Johnson DW. Increased stroke risk predicted by compromised cerebral blood flow reactivity. J Neurosurg. 1993;79:483–489.[Medline] [Order article via Infotrieve]
7. Webster MW, Makaroun MS, Steed DL, Smith HA, Johnson DW, Yonas H. Compromised cerebral blood flow reactivity is a predictor of stroke in patients with symptomatic carotid artery occlusive disease. J Vasc Surg. 1995;21:338–345.[Medline] [Order article via Infotrieve]
8.
Yamauchi H, Fukuyama H, Nagahama Y, Nabatame H,
Nakamura K, Yamamoto Y, Yonekura Y, Konishi J, Kimura J. Evidence for
misery perfusion and risk for recurrent stroke in major cerebral
arterial occlusive diseases from PET. J Neurol
Neurosurg Psychiatry. 1996;61:18–25.
9.
Bornstein NM, Norris JW. Benign outcome of carotid
occlusion. Neurology. 1989;39:6–8.
10.
Hennerici M, Hulsbomer HB, Rautenberg W, Hefter H.
Spontaneous history of asymptomatic internal carotid
occlusion. Stroke. 1986;17:718–722.
11. Derdeyn CP, Yundt KD, Videen TO, Carpenter DA, Grubb RL, Powers WJ. Increased oxygen extraction fraction is associated with prior ischemic events in patients with carotid artery occlusion. Stroke. 1998;29:745–758.
12.
Aaslid R, Lindegaard KF, Sorteberg W, Nornes H.
Cerebral autoregulation dynamics in humans. Stroke. 1989;20:45–52.
13. Aaslid R, Markwalder TM, Nornes H. Non-invasive transcranial Doppler ultrasound recording of flow velocity in basal cerebral arteries. J Neurosurg. 1982;57:769–774.[Medline] [Order article via Infotrieve]
14.
Bishop CCR, Powell S, Rutt D, Browse NL.
Transcranial Doppler measurement of middle cerebral
artery blood flow velocity: a validation study. Stroke. 1986;17:913–915.
15.
Ringelstein EB, Sievers C, Ecker S, Schneider PA, Otis
SM. Noninvasive assessment of CO2-induced
cerebral vasomotor response in normal individuals and patients with
internal carotid artery occlusion. Stroke. 1988;19:963–969.
16. Ringelstein EB, Van Eyck S, Mertens I. Evaluation of cerebral vasomotor reactivity by various vasodilating stimuli: comparison of CO2 to acetazolamide. J Cereb Blood Flow. 1992;12:162–168.[Medline] [Order article via Infotrieve]
17. Gortler M, Niethammer R, Widder B. Differentiating subtotal carotid artery stenoses from occlusion by color-coded duplex sonography. J Neurol. 1994;241:301–305.[Medline] [Order article via Infotrieve]
18. De Bray JM, Glatt B. Quantification of atheromatous stenosis in the extracranial internal carotid artery. Cerebrovasc Dis. 1995;5:414–426.
19. Bartels E. Vertebral sonography. In: Tagler CH, Babikian VL, Gomez CR, eds. Neurosonology. St Louis:Mosby;1996:83–100.
20. North American Symptomatic Carotid Endarterectomy Trial Collaborators. Beneficial effect of carotid endarterectomy in symptomatic patients with high-grade carotid stenosis. N Engl J Med. 1991;325:445–453.[Abstract]
21. Silvestrini M, Troisi E, Matteis M, Cupini LM, Bernardi G. Effect of smoking on cerebrovascular reactivity. J Cereb Blood Flow Metab. 1996;16:746–749.[Medline] [Order article via Infotrieve]
22.
Markus HS, Harrison MJ. Estimation of cerebrovascular
reactivity using transcranial Doppler, including the
use of breath-holding as the vasodilatatory stimulus.
Stroke. 1992;23:668–673.
23.
Coyle P, Panzenbeck MJ. Collateral development after
carotid artery occlusion in Fischer 344 rats. Stroke. 1990;21:316–321.
24. Widder B, Kleiser B, Krapf H. Course of cerebrovascular reactivity in patients with carotid artery occlusion. Stroke. 1994;25:1963–1967.[Abstract]
25. Widder B, Kornhuber HH. Extra-intracranial bypass surgery in carotid artery occlusions: who benefits? Neurol Psych Brain Res. 1994;2:126–131.
26. Hedera P, Bujdakova J, Traubner P. Compressions of carotid and vertebral arteries in assessment of intracranial collateral flow: correlation between angiography and transcranial Doppler ultrasonography. Angiology. 1994;45:1039–1045.
27. Hedera P, Bujdakova J, Traubner P. Effect of collateral flow patterns on outcome of carotid occlusion. Eur Neurol. 1995;35:212–216.[Medline] [Order article via Infotrieve]
28.
Anzola GP, Gasparotti R, Magoni M, Prandini F.
Transcranial Doppler sonography and magnetic resonance
angiography in the assessment of collateral hemispheric flow in
patients with carotid artery disease. Stroke. 1995;26:214–217.
29. Bladin C, Chambers BR. Frequency and pathogenesis of hemodynamic stroke. Stroke. 1994;25:2179–2182.[Abstract]
30. Bamford JL, Sandercock PAG, Dennis M, Burn J, Warlow CP. Classification and natural history of clinically identifiable subtypes of cerebral infarction. Lancet. 1991;337:1521–1526.[Medline] [Order article via Infotrieve]
31. Sundt TM, Sharbrough FW, Anderson RE, Michenfelder JD. Cerebral blood flow measurements and electroencephalograms during carotid endarterectomy. J Neurosurg. 1974;41:310–320.[Medline] [Order article via Infotrieve]
32. The EC/IC Bypass Study Group. Failure of extracranial-intracranial arterial bypass to reduce the risk of ischemic stroke: results of an international randomized trial. N Engl J Med. 1985;313:1191–1200.[Abstract]
33.
Karnik R, Valentin A, Ammerer HP, Donath P, Slany J.
Evaluation of vasomotor reactivity by transcranial
Doppler and acetazolamide test before and after
extracranial-intracranial bypass in patients with internal carotid
artery occlusion. Stroke. 1992;23:812–817.
34. Klijn CJM, Kappelle LJ, van der Grond J, van Gijn J, Tulleken CAF. A new type of extracranial-intracranial bypass for recurrent hemodynamic transient ischemic attacks. Cerebrovasc Dis. 1998;8:184–187.[Medline] [Order article via Infotrieve]
This article has been cited by other articles:
 |
|
 |
|
  A.S. Vagal, J.L. Leach, M. Fernandez-Ulloa, and M. Zuccarello The Acetazolamide Challenge: Techniques and Applications in the Evaluation of Chronic Cerebral Ischemia AJNR Am. J. Neuroradiol., May 1, 2009; 30(5): 876 - 884. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Urbano, F. Roux, J. Schindler, and V. Mohsenin Impaired cerebral autoregulation in obstructive sleep apnea J Appl Physiol, December 1, 2008; 105(6): 1852 - 1857. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. J. Bos, P. J. Koudstaal, A. Hofman, J. C.M. Witteman, and M. M.B. Breteler Transcranial Doppler Hemodynamic Parameters and Risk of Stroke: The Rotterdam Study Stroke, September 1, 2007; 38(9): 2453 - 2458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Uzuner, S. Ozkan, and N. Cinar Cerebrovascular reactivity in multiple sclerosis patients Multiple Sclerosis, July 1, 2007; 13(6): 737 - 741. [Abstract] [PDF]
|
|
|
|
 |
|
 K. I. Paraskevas, D. P. Mikhailidis, and C. D. Liapis Internal Carotid Artery Occlusion: Association With Atherosclerotic Disease in Other Arterial Beds and Vascular Risk Factors Angiology, June 1, 2007; 58(3): 329 - 335. [Abstract] [PDF]
|
|
|
|
|
|
I. Momjian-Mayor and J.-C. Baron The Pathophysiology of Watershed Infarction in Internal Carotid Artery Disease: Review of Cerebral Perfusion Studies Stroke, March 1, 2005; 36(3): 567 - 577. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ogasawara, T. Inoue, M. Kobayashi, H. Endo, K. Yoshida, T. Fukuda, K. Terasaki, and A. Ogawa Cerebral Hyperperfusion Following Carotid Endarterectomy: Diagnostic Utility of Intraoperative Transcranial Doppler Ultrasonography Compared with Single-Photon Emission Computed Tomography Study AJNR Am. J. Neuroradiol., February 1, 2005; 26(2): 252 - 257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Kamouchi, K. Kishikawa, Y. Okada, T. Inoue, S. Ibayashi, and M. Iida Poststenotic Flow and Intracranial Hemodynamics in Patients with Carotid Stenosis: Transoral Carotid Ultrasonography Study AJNR Am. J. Neuroradiol., January 1, 2005; 26(1): 76 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. Neri, G. Sani, M. Massetti, G. Frati, D. Buklas, R. Tassi, M. Giubbolini, A. Benvenuti, and C. Sassi Residual dissection of the brachiocephalic arteries: Significance, management, and long-term outcome J. Thorac. Cardiovasc. Surg., August 1, 2004; 128(2): 303 - 312. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. N. Gundamraj and K. K. Lauer Diagnosis of Intracranial Arterial Stenosis Using Transcranial Doppler Flowmetry Anesth. Analg., June 1, 2004; 98(6): 1776 - 1778. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. J. de Boorder, J. Hendrikse, and J. van der Grond Phase-Contrast Magnetic Resonance Imaging Measurements of Cerebral Autoregulation With a Breath-Hold Challenge: A Feasibility Study Stroke, June 1, 2004; 35(6): 1350 - 1354. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. A. Sloan, A. V. Alexandrov, C. H. Tegeler, M. P. Spencer, L. R. Caplan, E. Feldmann, L. R. Wechsler, D. W. Newell, C. R. Gomez, V. L. Babikian, et al. Assessment: Transcranial Doppler ultrasonography: Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology Neurology, May 11, 2004; 62(9): 1468 - 1481. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. M. Rossini, C. Altamura, A. Ferretti, F. Vernieri, F. Zappasodi, M. Caulo, V. Pizzella, C. Del Gratta, G.-L. Romani, and F. Tecchio Does cerebrovascular disease affect the coupling between neuronal activity and local haemodynamics? Brain, January 1, 2004; 127(1): 99 - 110. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vernieri, F. Tibuzzi, P. Pasqualetti, N. Rosato, F. Passarelli, P. M. Rossini, and M. Silvestrini Transcranial Doppler and Near-Infrared Spectroscopy Can Evaluate the Hemodynamic Effect of Carotid Artery Occlusion Stroke, January 1, 2004; 35(1): 64 - 70. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P.M. Rothwell, S.C. Howard, and J.D. Spence Relationship Between Blood Pressure and Stroke Risk in Patients With Symptomatic Carotid Occlusive Disease Stroke, November 1, 2003; 34(11): 2583 - 2590. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P Derdeyn Cerebral Hemodynamics in Carotid Occlusive Disease AJNR Am. J. Neuroradiol., September 1, 2003; 24(8): 1497 - 1499. [Full Text] [PDF]
|
|
|
|
|
|
R. S. Marshall, T. Rundek, D. M. Sproule, B.-F. M. Fitzsimmons, S. Schwartz, and R. M. Lazar Monitoring of Cerebral Vasodilatory Capacity With Transcranial Doppler Carbon Dioxide Inhalation in Patients With Severe Carotid Artery Disease Stroke, April 1, 2003; 34(4): 945 - 949. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Derdeyn, R. L. Grubb Jr, and W. J. Powers Re: Stages and Thresholds of Hemodynamic Failure Stroke, March 1, 2003; 34(3): 589 - 589. [Full Text] [PDF]
|
|
|
|
|
|
D.R. Rutgers, M.J.P. van Osch, L.J. Kappelle, W.P.T.M. Mali, and J. van der Grond Cerebral Hemodynamics and Metabolism in Patients With Symptomatic Occlusion of the Internal Carotid Artery Stroke, March 1, 2003; 34(3): 648 - 652. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J.M. Klijn, L. J. Kappelle, A. van der Zwan, J. van Gijn, and C. A.F. Tulleken Excimer Laser-Assisted High-Flow Extracranial/Intracranial Bypass in Patients With Symptomatic Carotid Artery Occlusion at High Risk of Recurrent Cerebral Ischemia: Safety and Long-Term Outcome Stroke, October 1, 2002; 33(10): 2451 - 2458. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Bozzao, R. Floris, F. Gaudiello, V. Finocchi, L. M. Fantozzi, and G. Simonetti Hemodynamic Modifications in Patients with Symptomatic Unilateral Stenosis of the Internal Carotid Artery: Evaluation with MR Imaging Perfusion Sequences AJNR Am. J. Neuroradiol., September 1, 2002; 23(8): 1342 - 1345. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Ogasawara, A. Ogawa, and T. Yoshimoto Cerebrovascular Reactivity to Acetazolamide and Outcome in Patients With Symptomatic Internal Carotid or Middle Cerebral Artery Occlusion: A Xenon-133 Single-Photon Emission Computed Tomography Study Stroke, July 1, 2002; 33(7): 1857 - 1862. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Blaser, K. Hofmann, T. Buerger, O. Effenberger, C.-W. Wallesch, and M. Goertler Risk of Stroke, Transient Ischemic Attack, and Vessel Occlusion Before Endarterectomy in Patients With Symptomatic Severe Carotid Stenosis Stroke, April 1, 2002; 33(4): 1057 - 1062. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. M. Barrett, R. H. Ackerman, G. Gahn, J. M. Romero, and M. Candia Basilar and Middle Cerebral Artery Reserve: A Comparative Study Using Transcranial Doppler and Breath-Holding Techniques Stroke, December 1, 2001; 32(12): 2793 - 2796. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Kuroda, K. Houkin, H. Kamiyama, K. Mitsumori, Y. Iwasaki, H. Abe, H. Yonas, L. R. Wechsler, E. Nemoto, and R. Pindzola Long-Term Prognosis of Medically Treated Patients With Internal Carotid or Middle Cerebral Artery Occlusion: Can Acetazolamide Test Predict It? Editorial Comment: Can Acetazolamide Test Predict It? Stroke, September 1, 2001; 32(9): 2110 - 2116. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. R. Pindzola, J. R. Balzer, E. M. Nemoto, S. Goldstein, and H. Yonas Cerebrovascular Reserve in Patients With Carotid Occlusive Disease Assessed by Stable Xenon-Enhanced CT Cerebral Blood Flow and Transcranial Doppler Stroke, August 1, 2001; 32(8): 1811 - 1817. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Vernieri, P. Pasqualetti, M. Matteis, F. Passarelli, E. Troisi, P. M. Rossini, C. Caltagirone, and M. Silvestrini Effect of Collateral Blood Flow and Cerebral Vasomotor Reactivity on the Outcome of Carotid Artery Occlusion Stroke, July 1, 2001; 32(7): 1552 - 1558. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Apruzzese, M. Silvestrini, R. Floris, F. Vernieri, A. Bozzao, G. Hagberg, C. Caltagirone, S. Masala, and G. Simonetti Cerebral Hemodynamics in Asymptomatic Patients with Internal Carotid Artery Occlusion: A Dynamic Susceptibility Contrast MR and Transcranial Doppler Study AJNR Am. J. Neuroradiol., June 1, 2001; 22(6): 1062 - 1067. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Rohrberg and R. Brodhun Measurement of Vasomotor Reserve in the Transcranial Doppler-CO2 Test Using an Ultrasound Contrast Agent (Levovist) Stroke, June 1, 2001; 32(6): 1298 - 1303. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Markus and M. Cullinane Severely impaired cerebrovascular reactivity predicts stroke and TIA risk in patients with carotid artery stenosis and occlusion Brain, March 1, 2001; 124(3): 457 - 467. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. R. Rutgers, C. J. M. Klijn, L. J. Kappelle, B. C. Eikelboom, A. C. van Huffelen, and J. van der Grond Sustained Bilateral Hemodynamic Benefit of Contralateral Carotid Endarterectomy in Patients With Symptomatic Internal Carotid Artery Occlusion Stroke, March 1, 2001; 32(3): 728 - 734. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Miyazawa, K. Hashizume, M. Uchida, and H. Nukui Long-term Follow-up of Asymptomatic Patients with Major Artery Occlusion: Rate of Symptomatic Change and Evaluation of Cerebral Hemodynamics AJNR Am. J. Neuroradiol., February 1, 2001; 22(2): 243 - 247. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. M. Klijn, L. J. Kappelle, A. C. van Huffelen, G. H. Visser, A. Algra, C. A. F. Tulleken, and J. van Gijn Recurrent ischemia in symptomatic carotid occlusion: Prognostic value of hemodynamic factors Neurology, December 26, 2000; 55(12): 1806 - 1812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. J. M. Klijn, L. J. Kappelle, J. van der Grond, A. Algra, C. A. F. Tulleken, and J. van Gijn Magnetic Resonance Techniques for the Identification of Patients With Symptomatic Carotid Artery Occlusion at High Risk of Cerebral Ischemic Events Stroke, December 1, 2000; 31(12): 3001 - 3007. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Tegos, M. Sohail, M. M. Sabetai, P. Robless, N. Akbar, G. Pare, G. Stansby, and A. N. Nicolaides Echomorphologic and Histopathologic Characteristics of Unstable Carotid Plaques AJNR Am. J. Neuroradiol., November 1, 2000; 21(10): 1937 - 1944. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. J. Tegos, E. Kalodiki, S.-S. Daskalopoulou, and A. N. Nicolaides Stroke: Epidemiology, Clinical Picture, and Risk Factors: Part I of III Angiology, October 1, 2000; 51(10): 793 - 808. [Abstract] [PDF]
|
|
|
|
|
|
D. R. Rutgers, C. J. M. Klijn, L. J. Kappelle, A. C. van Huffelen, and J. van der Grond A Longitudinal Study of Collateral Flow Patterns in the Circle of Willis and the Ophthalmic Artery in Patients With a Symptomatic Internal Carotid Artery Occlusion Stroke, August 1, 2000; 31(8): 1913 - 1920. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Silvestrini, F. Vernieri, P. Pasqualetti, M. Matteis, F. Passarelli, E. Troisi, and C. Caltagirone Impaired Cerebral Vasoreactivity and Risk of Stroke in Patients With Asymptomatic Carotid Artery Stenosis JAMA, April 26, 2000; 283(16): 2122 - 2127. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. R. Lash and C. P. Derdeyn Cerebral hemodynamic impairment: Methods of measurement in association with stroke Neurology, March 14, 2000; 54(5): 1210 - 1210. [Full Text] [PDF]
|
|
|
|
|
|
P. M. Rothwell and C. P. Warlow Low Risk of Ischemic Stroke in Patients With Reduced Internal Carotid Artery Lumen Diameter Distal to Severe Symptomatic Carotid Stenosis : Cerebral Protection Due to Low Poststenotic Flow? Stroke, March 1, 2000; 31(3): 622 - 630. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. J. Powers, C. P. Derdeyn, S. M. Fritsch, D. A. Carpenter, K. D. Yundt, T. O. Videen, and R. L. Grubb Jr. Benign prognosis of never-symptomatic carotid occlusion Neurology, February 22, 2000; 54(4): 878 - 882. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. T.F. Cheung, M. Silvestrini, F. Vernieri, and P. Pasqualetti Cerebrovascular Reactivity in Internal Carotid Artery Occlusion • Response Stroke, December 1, 1999; 30 (12): 2759 - 2768. [Full Text] [PDF]
|
|
|
|
|
|
C. Molina, J. A. Sabin, J. Montaner, A. Rovira, S. Abilleira, and A. Codina Impaired Cerebrovascular Reactivity as a Risk Marker for First-Ever Lacunar Infarction : A Case-Control Study Stroke, November 1, 1999; 30 (11): 2296 - 2301. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. P. Derdeyn, R. L. Grubb Jr., and W. J. Powers Cerebral hemodynamic impairment: Methods of measurement and association with stroke risk Neurology, July 1, 1999; 53(2): 251 - 251. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||