Background and purpose
NOTCH3 p.R544C mutation accounts for 5% of spontaneous intracerebral haemorrhage (ICH) in East Asian patients. We investigated whether certain CT features are associated with NOTCH3-related ICH.
Patients with spontaneous ICH from a prospective stroke registry were screened for NOTCH3 p.R544C mutation. The neuroimaging features on the initial non-contrast CT scans selected to predict NOTCH3 p.R544C mutation, including burden of white matter lesion (WML), degree of brain atrophy, number of lacunes, prominent juxtacortical WML and prominent lobar lacunes, were analysed by neuroradiologists blinded to the mutation status.
Of 299 patients with spontaneous ICH (mean age, 61 years; male, 68%; ICH volumes, 14.1±17.8 mL), 13 patients (4.3%) carried NOTCH3 p.R544C mutation. The clinical features, haematoma size and location were similar between NOTCH3 p.R544C mutation carriers and non-carriers. The CT scan revealed that patients with NOTCH3 p.R544C mutation had more severe WML and more frequently had prominent juxtacortical WML (69.2% vs 17.8%, p<0.001), and the effects were not driven by ageing as seen in patients without mutation. Prominent juxtacortical WML (area under receiver operating characteristic curve=0.76) outperformed the total WML score and prominent lobar lacunes and significantly predicted NOTCH3 p.R544C mutation in a multivariable-adjusted model (OR, 20.9; 95% CI 4.94 to 88.6).
In patients with spontaneous ICH, the severity and topographic distribution of WML can help in identifying potential NOTCH3 mutation-related ICH.