Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Comparative Study
. 2021 Nov;41(11):3039-3051.
doi: 10.1177/0271678X211024373. Epub 2021 Jun 10.

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

Martina Sebök  1   2 , Christiaan Hendrik Bas van Niftrik  1   2 , Niklas Lohaus  2   3 , Giuseppe Esposito  1   2 , Mohamad El Amki  2   4 , Sebastian Winklhofer  2   3 , Susanne Wegener  2   4 , Luca Regli  1   2 , Jorn Fierstra  1   2
Affiliations
Comparative Study

Leptomeningeal collateral activation indicates severely impaired cerebrovascular reserve capacity in patients with symptomatic unilateral carotid artery occlusion

Martina Sebök et al. J Cereb Blood Flow Metab. 2021 Nov.

Abstract

For patients with symptomatic unilateral internal carotid artery (ICA) occlusion, impaired cerebrovascular reactivity (CVR) indicates increased stroke risk. Here, the role of collateral activation remains a matter of debate, whereas angio-anatomical collateral abundancy does not necessarily imply sufficient compensatory flow provided. We aimed to further elucidate the role of collateral activation in the presence of impaired CVR. From a prospective database, 62 patients with symptomatic unilateral ICA occlusion underwent blood oxygenation-level dependent (BOLD) fMRI CVR imaging and a transcranial Doppler (TCD) investigation for primary and secondary collateral activation. Descriptive statistic and multivariate analysis were used to evaluate the relationship between BOLD-CVR values and collateral activation. Patients with activated secondary collaterals exhibited more impaired BOLD-CVR values of the ipsilateral hemisphere (p = 0.02). Specifically, activation of leptomeningeal collaterals showed severely impaired ipsilateral hemisphere BOLD-CVR values when compared to activation of ophthalmic collaterals (0.05 ± 0.09 vs. 0.12 ± 0.04, p = 0.005). Moreover, the prediction analysis showed leptomeningeal collateral activation as a strong independent predictor for ipsilateral hemispheric BOLD-CVR. In our study, ipsilateral leptomeningeal collateral activation is the sole collateral pathway associated with severely impaired BOLD-CVR in patients with symptomatic unilateral ICA occlusion.

Keywords: BOLD fMRI; TCD; carotid artery occlusion; cerebrovascular reactivity; collaterals.

PubMed Disclaimer

Conflict of interest statement

Declaration of conflicting interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
Study flow chart. From 150 patients with symptomatic carotid artery disease included in our prospective BOLD-CVR database, 85 patients were diagnosed with symptomatic carotid artery occlusion. Out of them, 68 patients presented with untreated symptomatic unilateral (maximal stenosis of 50% of the contralateral ICA) carotid artery occlusion and underwent a BOLD-CVR study and were available for inclusion in this prospective cohort study. In six patients out of 68, no TCD study was available. In the final analysis, 62 patients with untreated unilateral symptomatic ICA occlusion, who underwent both, BOLD-CVR and TCD investigation, were included. BOLD: blood oxygen-level dependent; CVR: cerebrovascular reactivity; ICA: internal carotid artery; TCD: transcranial Doppler.
Figure 2.
Figure 2.
Schematic representation of collateral pathways and exemplary BOLD-CVR images of two patients with right ICA occlusion. (a) The figure shows the available four collateral pathways (two primary collaterals and two secondary collaterals) in patients with unilateral ICA occlusion. The two primary collaterals, which are part of the Circle of Willis, are ACOM and PCOM. Activation of ACOM is detected as reversed flow direction in the first (A1) segment of the anterior cerebral artery ipsilateral to the occluded ICA. Activation of PCOM is identified as cerebral blood flow increase of > 50% in the ipsilateral first (P1) segment of the posterior cerebral artery compared with the contralateral side. The two TCD-derived secondary collaterals are ophthalmic and leptomeningeal collaterals supplied by the posterior circulation. Activation of ophthalmic collaterals is detected as reversed flow in the periorbital arteries and activation of leptomeningeal collaterals as flow increase of > 30% in the ipsilateral second (P2) segment of posterior cerebral artery compared with the contralateral P2 segment. (B) The figure shows activation of leptomeningeal collaterals on the surface of the ipsilateral (=side of ICA occlusion) hemisphere with impaired (=paradox) CVR in this hemisphere. (c) BOLD-CVR image of a 48-years old patient with occlusion of right ICA showed preserved CVR in the territory of the occluded vessel. The TCD examination showed only primary activation through ACOM with reversed flow direction in the right ACA-A1 segment. (d) BOLD-CVR image of 85-years old patient with occlusion of right ICA showed impaired CVR in the territory of the occluded vessel. The TCD examination showed: 1) right sided PCOM activation with 184% increase of SFV of the right PCA-P1 segment compared to the contralateral PCA-P1, 2) reversed flow in the right ophthalmic artery indicating right sided ophthalmic activation, and 3) activation of leptomeningeal collateral pathways supplied by the posterior circulation on the ride side with 130% increase of SFV of the right PCA-P2 segment compared to the contralateral PCA-P2. ACA-A1: first segment of anterior cerebral artery; ACOM: anterior communicating artery; BOLD: blood oxygenation-level dependent; CVR: cerebrovascular reactivity; ICA: internal carotid artery; PCA-P1: first segment of posterior cerebral artery; PCA-P2: second segment of posterior cerebral artery; PCOM: posterior communicating artery; SFV: systolic flow velocity; TCD: transcranial Doppler.
Figure 3.
Figure 3.
Correlation between percentage of activated available collaterals and mean ipsilateral hemisphere BOLD-CVR values. Box-whisker plots show the correlation between the percentages of activated available collaterals and mean BOLD-CVR values of the ipsilateral hemisphere. Patients with more activated collaterals exhibit significantly lower CVR values: patients with 75% and 100% of activated available collaterals have significantly lower mean BOLD-CVR of ipsilateral hemisphere as compared to patients with activated 25-33% of available collaterals; patients with 100% collateral activation exhibit significantly lower CVR values compared to patients with 50-67% collateral activation. Activation of maximal four collateral pathways (ACOM, PCOM, ophthalmic artery, and leptomeningeal collateral pathways supplied by the posterior circulation) is possible. However, after anatomical correction there are also patients with only three or two anatomically possible collaterals. Therefore, the quotient between activated collaterals in TCD and possible collaterals in anatomical images is always calculated for the corrected number of anatomical collaterals. For example: in patient with three possible collaterals as seen in TOF MRA and activation of two of those collaterals in TCD, the percentage of activated collaterals is calculated as: 2/3 * 100% = 67%. Patients with activation of 1/4 and 1/3 of anatomically available collaterals form the 25-33% group and patients with activation of 1/2 and 2/3 of anatomically available the 50-67% group. Note: The box of box-whisker plots represents the median value with interquartile range (25th to the 75th percentile). The upper and lower whiskers represent values outside the middle 50% (i.e., the values below 25th and above 75th percentile). BOLD: blood oxygen-level dependent; CVR: cerebrovascular reactivity.
Figure 4.
Figure 4.
Correlation between different stages of secondary collaterals activation and mean ipsilateral hemisphere BOLD-CVR values. Box-whisker plots show the correlation between the three groups of patients with different secondary collaterals activation status and BOLD-CVR values of ipsilateral hemisphere. Patients with activated leptomeningeal collateral pathways supplied by the posterior circulation with/without activation of ophthalmic collaterals (group 3) exhibit significantly lower mean BOLD-CVR values of ipsilateral hemisphere compared to patients without any secondary collaterals (group 1) (mean BOLD-CVR ± SD: 0.05±0.09 vs. 0.13±0.05, p=0.003) as well as compared to patients with activation of only ophthalmic collaterals (group 2) (mean BOLD-CVR ± SD: 0.05±0.09 vs. 0.12±0.04, p=0.005). No difference is BOLD-CVR values is discernible between patients without any activated secondary collaterals and between patients with only ophthalmic activation. The between groups difference for ipsilateral BOLD-CVR values by one-way ANOVA is p=0.001. Note: The box of box-whisker plots represents the median value with interquartile range (25th to the 75th percentile). The upper and lower whiskers represent values outside the middle 50% (i.e., the values below 25th and above 75th percentile). ANOVA: analysis of variance; BOLD: blood oxygen-level dependent; CVR: cerebrovascular reactivity; SD: standard deviation.
Figure 5.
Figure 5.
Correlation between different stages of PCOM and leptomeningeal collaterals activation and mean ipsilateral hemisphere BOLD-CVR values. Box-whisker plots show the correlation between the groups of patients with different activation status of PCOM and leptomeningeal collateral pathways supplied by the posterior circulation and BOLD-CVR values of ipsilateral hemisphere. Patients with activated both, PCOM and leptomeningeal collaterals (group 4) exhibit significantly lower mean BOLD-CVR values of ipsilateral hemisphere compared to patients with only PCOM activation (group 2) (mean BOLD-CVR ± SD: -0.01±0.06 vs. 0.12±0.06, p=0.003) and patients with only leptomeningeal activation (group 3) (mean BOLD-CVR ± SD: mean BOLD-CVR ± SD: -0.01±0.06 vs. 0.07±0.09, p=0.03). The between groups difference for ipsilateral BOLD-CVR values by one-way ANOVA is p<0.001. Note: The box of box-whisker plots represents the median value with interquartile range (25th to the 75th percentile). The upper and lower whiskers represent values outside the middle 50% (i.e., the values below 25th and above 75th percentile). ANOVA: analysis of variance; BOLD: blood oxygen-level dependent; CVR: cerebrovascular reactivity; PCOM: posterior communicating artery; SD: standard deviation.
See this image and copyright information in PMC

References

    1. Flaherty ML, Flemming KD, McClelland R, et al. Population-based study of symptomatic internal carotid artery occlusion: incidence and long-term follow-up. Stroke 2004; 35: e349-52. - PubMed
    1. Reinhard M, Schwarzer G, Briel M, et al. Cerebrovascular reactivity predicts stroke in high-grade carotid artery disease. Neurology 2014; 83: 1424–1431. - PMC - PubMed
    1. Papassin J, Heck O, Condamine E, et al. Impaired cerebrovascular reactivity is associated with recurrent stroke in patients with severe intracranial arterial stenosis: a C02 BOLD fMRI study. J Neuroradiol 2020; S0150-9861(20)30165-6. - PubMed
    1. Müller M, andSchimrigk K.. Vasomotor reactivity and pattern of collateral blood flow in severe occlusive carotid artery disease. Stroke 1996; 27: 296–299. - PubMed
    1. Schomer DF, Marks MP, Steinberg GK, et al. The anatomy of the posterior communicating artery as a risk factor for ischemic cerebral infarction. N Engl J Med 1994; 330: 1565–1570. - PubMed

Publication types

MeSH terms