Table 1: Summary of clinical studies evaluating cerebrovascular reserve in patients with internal carotid artery atherosclerotic lesions.

Author, year Type of study Number of patients Clinical course of desease Severity of ICA lesion CO2-reactivity DCA assessment Blood flow measurement Findings
Ringelstein E [10] Cohort 40 Asymptomatic/ Symptomatic Occlusion Vasodilatory response of CO2/ acetazolamide, hyperventilation TCD The difference between vasomotor reactivity for symptomatic and asymptomatic unilateral occlusions was highly significant.
Kleiser B [17] Cohort 85 Asymptomatic/ Symptomatic Occlusion Inhalation of 5% CO2, hyperventilation TCD CO2 test is a valuable method of estimating the risk of stroke in patients with carotid artery occlusions.
Yonas H [18] Cohort 68 Symptomatic Stenosis ≥ 75% or occlusion Acetazolamide Xe/CT Compromised CO2 reactivity accompanied by relatively low initial flow significantly increased incidence of ipsilateral stroke.
Gur A [19] Cohort 44 Asymptomatic Stenosis ≥ 70% or occlusion Acetazolamide TCD Statistically significant correlation between cerebral ischemic events and impaired cerebral vasomotor reactivity
White R [12] Cohort 27 Asymptomatic Stenosis ≥ 60% or occlusion Inhalation of 8% CO2 Autoregulation index (ARI) with cuff-test TCD ARI significantly reduced in ipsilateral MCA compared with normal controls and nonstenosed carotid arteries in patients.
Hu H., 1999 [13] Cohort 83 Symptomatic Stenosis or occlusion Inhalation of 5% CO2 Phase angle between BP and BFV at diiferent frequency ranges (frequency domain) TCD Patients with unilateral high-grade carotid stenosis demonstrated significant reduction in LF (0.04-0.15 Hz) phase angle, CO2-reactivity.
Vernieri F [24] Cohort 104 Asymptomatic/ Symptomatic Breath-holding index TCD Risk of cerebrovascular events occurring during the follow-up period was significantly related to vasomotor reactivity and type of collateral pathway
Reinhard M [8] Cohort 101 Asymptomatic/ Symptomatic Stenosis ≥ 70% or occlusion Inhalation of 7% CO2 PS between BP and BFV at 0.1 Hz (frequency domain) TCD Strong association between type of collateral flow and CO2-reactitvity, PS.
Reinhard M [11] Cohort 139 Asymptomatic/ Symptomatic Stenosis ≥ 70% or occlusion Inhalation of 7% CO2 PS shift between BP and BFV at 0.1 Hz (frequency domain); Correlation coefficient indexes between BP and BFV (time domain) TCD The correlation indexes Dx and Mx were significantly higher ipsilateral to stenosis and increased with degree of stenosis.
Reinhard M [14] Cohort 58 Asymptomatic/ Symptomatic Stenosis ≥ 70% Inhalation of 7% CO2 PS shift between BP and BFV at 0.1 Hz (frequency domain); Correlation coefficient indexes between BP and BFV (time domain) TCD Reconstructive surgery led to reliable improvement of impaired CO2 reactivity and DCA ipsilaterally in severe carotid stenosis.
Tang S [15] Cohort 21 Asymptomatic/ Symptomatic Stenosis ≥ 50% Correlation coefficient indexes (Mx) between BP and BFV (time domain) TCD High correlation between the degree of ICA stenosis and the Mx. It improved significantly after carotid stenting in both moderate and severe ICA stenosis.
King A [7] Cohort Meta-analysis 106 Asymptomatic Stenosis ≥ 70% Vasodilatory response of CO2 or acetazolamide TCD No association between impaired CVR and recurrent events, but the study was underpowered because of the low event rate.
Gupta A [6] Meta-analysis 991 Asymptomatic/ symptomatic Stenosis or occlusion Vasodilatory response of CO2 or acetazolamide No TCD
SPECT
PET
CVR impairment is strongly associated with increased risk of ischemic events in carotid stenosis or occlusion.
Semenyutin V [16] Cohort 35 Asymptomatic/ Symptomatic Stenosis ≥ 75% PS shift between BP and BFV at 0.08-0.12 Hz (frequency domain) TCD Regardless clinical type of disease various state of DCA may be present in patients with severe ICA stenosis. Surgical reconstruction led to reliable restoration of impaired DCA.
Abbreviations: CVR: Cerebrovascular Reserve; ICA: Internal Carotid Artery; DCA: Dynamic Cerebral Autoregulation; PS: Phase Shift; BP: Blood Pressure; MCA: Middle Cerebral Artery; BFV: Blood Flow Velocity; LF: Low Frequency; TCD: Transcranial Doppler; Xe/CT: Xenon Computed Tomography; PET: Positron Emission Tomography; SPECT: Single-Photon Emission –°omputed Tomography