Universität zu Köln

Albanna, Walid, Conzen, Catharina, Weiss, Miriam ORCID: 0000-0001-8820-0805, Seyfried, Katharina, Kotliar, Konstantin, Schmidt, Tobias Philip, Kuerten, David, Hescheler, Jurgen, Bruecken, Anne, Schmidt-Trucksass, Arno ORCID: 0000-0002-4662-3911, Neumaier, Felix ORCID: 0000-0002-6376-6391, Wiesmann, Martin, Clusmann, Hans and Schubert, Gerrit Alexander (2021). Non-invasive Assessment of Neurovascular Coupling After Aneurysmal Subarachnoid Hemorrhage: A Prospective Observational Trial Using Retinal Vessel Analysis. Front. Neurol., 12. LAUSANNE: FRONTIERS MEDIA SA. ISSN 1664-2295

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Abstract

Objective: Delayed cerebral ischemia (DCI) is a common complication after aneurysmal subarachnoid hemorrhage (aSAH) and can lead to infarction and poor clinical outcome. The underlying mechanisms are still incompletely understood, but animal models indicate that vasoactive metabolites and inflammatory cytokines produced within the subarachnoid space may progressively impair and partially invert neurovascular coupling (NVC) in the brain. Because cerebral and retinal microvasculature are governed by comparable regulatory mechanisms and may be connected by perivascular pathways, retinal vascular changes are increasingly recognized as a potential surrogate for altered NVC in the brain. Here, we used non-invasive retinal vessel analysis (RVA) to assess microvascular function in aSAH patients at different times after the ictus. Methods: Static and dynamic RVA were performed using a Retinal Vessel Analyzer (IMEDOS Systems GmbH, Jena) in 70 aSAH patients during the early (d(0-4)), critical (d(5-15)), late (d(16-23)) phase, and at follow-up (f/u > 6 weeks) after the ictus. For comparison, an age-matched cohort of 42 healthy subjects was also included in the study. Vessel diameters were quantified in terms of the central retinal arterial and venous equivalent (CRAE, CRVE) and the retinal arterio-venous-ratio (AVR). Vessel responses to flicker light excitation (FLE) were quantified by recording the maximum arterial and venous dilation (MAD, MVD), the time to 30% and 100% of maximum dilation (tMAD(30), tMVD(30); tMAD, tMVD, resp.), and the arterial and venous area under the curve (AUC(art), AUC(ven)) during the FLE. For subgroup analyses, patients were stratified according to the development of DCI and clinical outcomes after 12 months. Results: Vessel diameter (CRAE, CRVE) was significantly smaller in aSAH patients and showed little change throughout the whole observation period (p < 0.0001 vs. control for all time periods examined). In addition, aSAH patients exhibited impaired arterial but not venous responses to FLE, as reflected in a significantly lower MAD [2.2 (1.0-3.2)% vs. 3.6 (2.6-5.6)% in control subjects, p = 0.0016] and AUC(art) [21.5 (9.4-35.8)%*s vs. 51.4 (32.5-69.7)%*s in control subjects, p = 0.0001] on d(0-4). However, gradual recovery was observed during the first 3 weeks, with close to normal levels at follow-up, when MAD and AUC(art) amounted to 3.0 [2.0-5.0]% (p = 0.141 vs. control, p = 0.0321 vs. d(5-15)) and 44.5 [23.2-61.1]%*s (p = 0.138 vs. control, p < 0.01 vs. d(0-4) & d(5-15)). Finally, patients with clinical deterioration (DCI) showed opposite changes in the kinetics of arterial responses during early and late phase, as reflected in a significantly lower tMAD(30) on d(0-4) [4.0 (3.0-6.8) s vs. 7.0 (5.0-8.0) s in patients without DCI, p = 0.022) and a significantly higher tMAD on d(16-23) (24.0 (21.0-29.3) s vs. 18.0 (14.0-21.0) s in patients without DCI, p = 0.017]. Conclusion: Our findings confirm and extend previous observations that aSAH results in sustained impairments of NVC in the retina. DCI may be associated with characteristic changes in the kinetics of retinal arterial responses. However, further studies will be required to determine their clinical implications and to assess if they can be used to identify patients at risk of developing DCI.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Albanna, Walid UNSPECIFIED UNSPECIFIED UNSPECIFIED Conzen, Catharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Weiss, Miriam UNSPECIFIED orcid.org/0000-0001-8820-0805 UNSPECIFIED Seyfried, Katharina UNSPECIFIED UNSPECIFIED UNSPECIFIED Kotliar, Konstantin UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt, Tobias Philip UNSPECIFIED UNSPECIFIED UNSPECIFIED Kuerten, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Hescheler, Jurgen UNSPECIFIED UNSPECIFIED UNSPECIFIED Bruecken, Anne UNSPECIFIED UNSPECIFIED UNSPECIFIED Schmidt-Trucksass, Arno UNSPECIFIED orcid.org/0000-0002-4662-3911 UNSPECIFIED Neumaier, Felix UNSPECIFIED orcid.org/0000-0002-6376-6391 UNSPECIFIED Wiesmann, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Clusmann, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Schubert, Gerrit Alexander UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-583374
DOI:	10.3389/fneur.2021.690183
Journal or Publication Title:	Front. Neurol.
Volume:	12
Date:	2021
Publisher:	FRONTIERS MEDIA SA
Place of Publication:	LAUSANNE
ISSN:	1664-2295
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DELAYED CEREBRAL-ISCHEMIA; MULTIDISCIPLINARY CONSENSUS CONFERENCE; TIME-COURSE; VASOSPASM; RISK; VASOCONSTRICTION; IMPAIRMENT; BIOMARKERS; INVERSION; SPACES Multiple languages Clinical Neurology; Neurosciences Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/58337