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. 2025 May;32(5):e70174.
doi: 10.1111/ene.70174.

Data-Driven Clustering Approach to Identify Different Phenotypes of Primary Central Nervous System Vasculitis

Hubert de Boysson  1   2 , Ahmad Nehme  2   3 , Anais R Briant  4 , Sonia Alamowitch  5 , Achille Aouba  1   2 , Caroline Arquizan  6   7 , Grégoire Boulouis  8 , Jean Capron  9 , Barbara Casolla  10 , Christian Denier  11 , Nelly Dequatre  12 , Olivier Detante  13   14 , Laurent Derex  15 , Sophie Godard  16 , Cédric Gollion  17 , Benoit Guillon  18 , Lisa Humbertjean  19 , Clothilde Isabel  20 , Philippe Kerschen  21 , Laurent Kremer  22 , Nicolas Lambert  23 , Sylvain Lanthier  24 , Adil Maarouf  25 , Antoine Néel  26 , Thomas Papo  27 , Alexandre Y Poppe  28 , Alexis Régent  29 , Amina Sellimi  30 , Igor Sibon  31 , Benjamin Terrier  29 , Emmanuel Touzé  2   3 , Stéphane Vannier  32 , David Weisenburger-Lile  33 , Mathieu Zuber  34 , Jean-Jacques Parienti  4 , Christian Pagnoux  35 ; COVAC' PCNSV Study Group
Collaborators, Affiliations

Data-Driven Clustering Approach to Identify Different Phenotypes of Primary Central Nervous System Vasculitis

Hubert de Boysson et al. Eur J Neurol. 2025 May.

Abstract

Background: To determine whether hierarchical unsupervised cluster analysis identifies a phenotypic distinction in adult patients with primary CNS vasculitis (PCNSV).

Methods: An agglomerative hierarchical cluster analysis based on the Ward method was conducted, including 153 patients with complete baseline phenotypic characterization in the COVAC' registry.

Results: The hierarchical analysis identified two main clusters. In Cluster 1 (n = 109 patients, 71%), patients more frequently had a motor deficit (p = 0.039), ≥ 1 acute brain infarct (p < 0.001), and ≥ 1 intracranial stenosis on CT or MR angiogram (p < 0.001) than patients in Cluster 2 (n = 44 patients, 29%). Conversely, patients in Cluster 2 more frequently had seizures (p < 0.001), cognitive impairment (p = 0.002), gadolinium-enhanced parenchymal lesions (p < 0.001), leptomeningeal enhancement (p < 0.001), ≥ 1 cerebral microbleed (p < 0.001), and intracranial hemorrhage(s) (p < 0.001). In multivariable logistic regression, gadolinium-enhanced parenchymal lesions were significantly associated with Cluster 2 lesions (OR = 35.53 [95% CI: 3.91-322.81], p = 0.002). Conversely, ≥ 1 acute brain infarct was significantly associated with Cluster 1 (OR = 0.003 [95% CI: 0.01-0.03], p < 0.001). A CNS biopsy was positive in 11/40 (28%) patients from Cluster 1 and 35/37 (95%) patients from Cluster 2 (p < 0.001). At 12 months, functional independence (modified Rankin scale score ≤ 2) did not differ between the two groups (p = 0.17). Relapse and mortality rates did not differ between the clusters (p = 0.17 and p = 0.23, respectively).

Conclusion: This unsupervised analysis of a large PCNSV cohort identified two different clinical and radiological phenotypes with different diagnostic work-ups, which confirms the relevance of distinguishing PCNSV phenotypes according to the sizes of affected vessels.

Keywords: PCNSV; clusters; non‐supervised; phenotypes; primary CNS vasculitis.

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Conflict of interest statement

Hubert de Boysson reports receiving fees for serving on advisory boards from Roche‐Chugai and Novartis and lecture fees from Roche‐Chugai, Novartis, Fresenius Kabi, GlaxoSmithKline, Amicus therapeutics, and Sanofi. Christian Pagnoux reports receiving fees for serving on advisory boards from Chemocentryx, Otsuka, GlaxoSmithKline, AstraZeneca, Sanofi, and Hoffman‐La Roche; lecture fees from Hoffman‐La Roche and GlaxoSmithKline; and educational grant support from Hoffman‐La Roche, Otsuka, Pfizer, TEVA, Amgen, and GlaxoSmithKline. The other authors declare no conflicts of interest.

Figures

FIGURE 1
FIGURE 1
Cluster analysis. (A) Cluster dendrogram. Hierarchical clustering revealed two clusters. (B) Cluster plot showing patient distribution in the clusters.
FIGURE 2
FIGURE 2
Diagram showing the cluster distributions in patients with biopsy‐proven and angiogram‐based diagnoses.
FIGURE 3
FIGURE 3
Kaplan–Meier relapse‐free survival of the 153 patients with complete datasets in the registry from Cluster 1 (blue curve) and Cluster 2 (red curve).
See this image and copyright information in PMC

References

    1. Beuker C., Strunk D., Rawal R., et al., “Primary Angiitis of the CNS: A Systematic Review and Meta‐Analysis,” Neurology Neuroimmunology & Neuroinflammation 8 (2021): e1093. - PMC - PubMed
    1. Nehme A., Boulanger M., Aouba A., et al., “Diagnostic and Therapeutic Approach to Adult Central Nervous System Vasculitis,” Revista de Neurologia 178 (2022): 1041–1054. - PubMed
    1. Birnbaum J. and Hellmann D. B., “Primary Angiitis of the Central Nervous System,” Archives of Neurology 66 (2009): 704–709. - PubMed
    1. Hajj‐Ali R. A., Singhal A. B., Benseler S., Molloy E., and Calabrese L. H., “Primary Angiitis of the CNS,” Lancet Neurology 10 (2011): 561–572. - PubMed
    1. Agarwal A., Sharma J., Srivastava M. V. P., et al., “Primary CNS Vasculitis (PCNSV): A Cohort Study,” Scientific Reports 12 (2022): 13494. - PMC - PubMed

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