Characterisation of patients with intracerebral haemorrhage with mixed location haemorrhages: clinical and imaging features, CSF neurodegeneration markers and recurrence risk

Abstract Introduction The most frequent causes of ICH include arteriolosclerotic small vessel disease (aSVD-ICH) and cerebral amyloid angiopathy (CAA-ICH). The predominant underlying pathology and natural history of ICH patients with mixed deep and lobar location haemorrhages (MLH-ICH) remain insufficiently studied. Patients and methods We performed a retrospective analysis of consecutive patients with ICH admitted between 2018 and 2024 and selected patients without macrostructural cause of haemorrhage, with available magnetic resonance imaging. We compared clinical characteristics, imaging markers, cerebrospinal fluid (CSF) neurodegeneration markers and ICH recurrence in patients with CAA-ICH, MLH-ICH and aSVD-ICH. Results We included 217 patients (CAA-ICH = 87, MLH-ICH = 79, aSVD-ICH = 51), median age was 72 years (IQR = 60–79), and 85 patients were female (39.2%). Patients with MLH-ICH were younger than CAA-ICH patients (P = .009) but older than aSVD-ICH patients (P = .012). Absence of cortical superficial siderosis, absence of severe burden of enlarged perivascular spaces (EPVS) in the centrum semiovale, presence of severe burden of EPVS in the basal ganglia, presence of deep and lobar cerebellar microbleeds and presence of deep lacunes were independently associated with MLH-ICH. Patients with MLH-ICH had higher CSF amyloid β42 (median 719 vs 359 pg/mL, P .001) and amyloid β40 levels (median 9124 vs 6958 pg/mL, P = .010) than CAA-ICH patients. ICH recurrence was higher in CAA-ICH (10.0 per 100 person-years), followed by MLH-ICH (6.0 per 100 person-years) and aSVD-ICH (1.3 per 100 person-years) (P = .048). Discussion and Conclusions Neuroimaging features, CSF neurodegeneration markers and ICH recurrence risk suggest that CAA is not the predominant pathology in most cases of MLH-ICH.