Sex differences in aetiology of intracerebral haemorrhage and associated small vessel disease patterns

Causes of intracerebral haemorrhage (ICH), in particular cerebral small vessel disease (SVD), are a frequent subject of current research, yet the potential role of sex differences remains uncertain. Therefore, we aimed to investigate whether there are sex-related differences in aetiology, MRI features of SVD and risks of recurrent cerebrovascular events in patients with ICH.

We included patients from 2 large observational ICH study cohorts (London/UK, Graz/Austria) with available MRI. ICH aetiology was defined based on brain MRI, vascular imaging as well as clinical findings. Multivariable regression models were fitted to assess sex differences in aetiology, SVD MRI features and recurrent stroke events.

We identified 1043 patients (mean age 66 years, 58% male) with acute ICH. Males had a higher prevalence of cryptogenic ICH than females (aOR 1.53; 95% CI, 1.01-2.33). Males also had a higher rate of presence of any lacune (aOR 1.47; 95% CI, 1.11-1.94), severely enlarged perivascular spaces in the basal ganglia (aOR 1.45; 95% CI, 1.04-2.02) and presence of small asymptomatic diffusion-weighted imaging lesions (aOR 1.51; 95% CI, 1.06-2.15). There were no sex differences regarding recurrent ICH, incident ischaemic stroke or mortality.

The higher rate of presence of any lacune and enlarged perivascular spaces in men with ICH implies a higher severity of arteriolosclerosis. The mechanisms underlying the higher occurrence of cryptogenic ICH in men might include transient risk factors or incipient SVD.