Related Experiment Video
Updated: Sep 25, 2025
Author Spotlight: Assessing the Potential of Circulating Tumor Cells in Leptomeningeal Disease Research
Published on: March 29, 2024
The Epidermal Growth Factor Domain of the Mutation Does Not Appear to Influence Disease Progression in CADASIL When
J Lebenberg1,2, J-P Guichard3, A Guillonnet3
1the Centre de Neurologie Vasculaire Translationel (J.L., D.H., N.A., A.T., N.D.-G., H.C.), Assistance Publique-Hôpitaux de Paris, Hôpital Lariboisiere, Paris, France; L'Institut National de la Santé et de la RechercheMédicale INSERM U1141, Université Paris Cité, Paris, France.
Background And Purpose:
By studying the evolution of brain volume across the life span in male and female patients, we aimed to understand how sex, brain volume, and the epidermal growth factor repeat domain of the mutation, the 3 major determinants of disability in CADASIL, interact in driving disease evolution.
Materials And Methods:
We used validated methods to model the evolution of normalized brain volume with age in male and female patients using nonparametric regression in a large, monocentric cohort with prospectively collected clinical and high-resolution MR imaging data. We used k-means clustering to test for the presence of different clinical course profiles.
Results:
We included 229 patients (mean age, 53 [SD, 12] years; 130 women). Brain volume was larger in women (mean size, 1024 [SD, 62] cm3 versus 979 [SD, 50] cm3; P < .001) and decreased regularly. In men, the relationship between brain volume and age unexpectedly suggested an increase in brain volume around midlife. Cluster analyses showed that this finding was related to the presence of a group of older male patients with milder symptoms and larger brain volumes, similar to findings of age-matched women. This group did not show specific epidermal growth factor repeat domain distribution.
Conclusions:
Our results demonstrate a detrimental effect of male sex on brain volume throughout life in CADASIL. We identified a subgroup of male patients whose brain volume and clinical outcomes were similar to those of age-matched women. They did not have a specific distribution of the epidermal growth factor repeat domain, suggesting that yet-unidentified predictors may interact with sex and brain volume in driving disease evolution.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:38Mitogens and the Cell Cycle