Clustering of diagnostic MRI signs of cerebral microangiopathy and its relationship with markers of inflammation and angiogenesis

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OBJECTIVE

To perform cluster analysis of MRI signs of cerebral microangiopathy (small vessel disease, SVD) and to clarify the relationship between the isolated groups and circulating markers of inflammation and angiogenesis.

MATERIAL AND METHODS

The identification of groups of MRI signs (MRI types) using cluster hierarchical agglomerative analysis and iterative algorithm of k-means and assessment of their relationship with serum concentrations of tumor necrosis factor-α (TNF-α), transforming growth factor-β1 (TGF-β1), vascular endothelial growth factor-A (VEGF-A), hypoxia-inducible factor 1-α (HIF1-α) determined by ELISA were performed in 96 patients with SVD (STRIVE, 2013) (65 women, average age 60.91±6.57 years).

RESULTS

Cluster analysis of MRI signs identified two MRI types of SVD with Fazekas grade 3 of white matter hyperintensity (WMH). MRI type 1 (n=18; 6 women, mean age 59.1±6.8 years) and MRI type 2 (n=22, 15 f., mean age 63.5±6.2 years) did not differ by age, sex, severity of hypertension, presence of other risk factors. MRI type 1 had a statistically significantly more pronounced WMH in the periventricular regions, multiple lacunes and microbleeds, atrophy, severe cognitive impairment and gait disorders compared with MRI type 2. Its formation was associated with a decrease in VEGF-A level. MRI type 2 had the significantly more pronounced juxtacortical WMH, white matter lacunes, in the absence of microbleeds and atrophy, and less severe clinical manifestations compared with MRI type 1. Its formation was associated with an increase in TNF-α level.

CONCLUSION

Clustering of diagnostic MRI signs into MRI types of SVD with significant differences in the severity of clinical manifestations suggests the pathogenetic heterogeneity of age-related SVD. The relationship of MRI types with circulating markers of different mechanisms of vascular wall and brain damage indicates the dominant role of depletion of angiogenesis in the formation of MRI type 1 and increased inflammation in the formation of MRI type 2. Further studies are needed to clarify the criteria and diagnostic value of differentiation of MRI types of SVD, and also their mechanisms with the definition of pathogenetically justified prevention and treatment of various forms of SVD.

Keywords:

cerebral microangiopathy

small vessel disease

neuroimaging

white matter hyperintensity

tumor necrosis factor-alpha

vascular endothelial growth factor

Authors:

Dobrynina L.A.

Research Center of Neurology

ORCID: 0000-0001-9929-2725

Gnedovskaya E.V.

Research Center of Neurology

Zabitova M.R.

Research Center of Neurology

Kremneva E.I.

Research Center of Neurology

Shabalina A.A.

Research Center of Neurology

SPIN RSCI: 9414-9068
Scopus AuthorID: 59097027100
ResearcherID: B-2504-2018
ORCID: 0000-0001-9604-7775

Makarova A.G.

Research Center of Neurology

Tzipushtanova M.M.

Research Center of Neurology

Filatov A.S.

Research Center of Neurology

Kalashnikova L.A.

Research Center of Neurology

ORCID: 0000-0003-1142-0548

Krotenkova M.V.

Research Center of Neurology

Received:

13.10.2020

Accepted:

14.10.2020

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