Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

Maaike P Cliteur; Lotte Sondag; Axel Wolsink; Ingeborg Rasing; F J A Meijer; Wilmar M T Jolink; Marieke J H Wermer; Catharina J M Klijn; Floris H B M Schreuder

doi:10.3389/fneur.2022.949133

Cerebral small vessel disease and perihematomal edema formation in spontaneous intracerebral hemorrhage

Front Neurol. 2022 Jul 29:13:949133. doi: 10.3389/fneur.2022.949133. eCollection 2022.

Authors

Maaike P Cliteur¹, Lotte Sondag¹, Axel Wolsink¹, Ingeborg Rasing², F J A Meijer³, Wilmar M T Jolink⁴, Marieke J H Wermer², Catharina J M Klijn¹, Floris H B M Schreuder¹

Affiliations

¹ Department of Neurology, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Centre, Nijmegen, Netherlands.
² Department of Neurology & Neurosurgery, Leiden University Medical Center, Leiden, Netherlands.
³ Department of Medical Imaging, Radboud University Medical Centre, Nijmegen, Netherlands.
⁴ Department of Neurology, Isala Hospital, Zwolle, Netherlands.

Abstract

Objective: Blood-brain barrier (BBB) dysfunction is implicated in the pathophysiology of cerebral small vessel disease (cSVD)-related intracerebral hemorrhage (ICH). The formation of perihematomal edema (PHE) is presumed to reflect acute BBB permeability following ICH. We aimed to assess the association between cSVD burden and PHE formation in patients with spontaneous ICH.

Methods: We selected patients with spontaneous ICH who underwent 3T MRI imaging within 21 days after symptom onset from a prospective observational multicenter cohort study. We rated markers of cSVD (white matter hyperintensities, enlarged perivascular spaces, lacunes and cerebral microbleeds) and calculated the composite score as a measure of the total cSVD burden. Perihematomal edema formation was measured using the edema extension distance (EED). We assessed the association between the cSVD burden and the EED using a multivariable linear regression model adjusting for age, (log-transformed) ICH volume, ICH location (lobar vs. non-lobar), and interval between symptom onset and MRI.

Results: We included 85 patients (mean age 63.5 years, 75.3% male). Median interval between symptom onset and MRI imaging was 6 days (IQR 1-19). Median ICH volume was 17.0 mL (IQR 1.4-88.6), and mean EED was 0.54 cm (SD 0.17). We found no association between the total cSVD burden and EED (B = -0.003, 95% CI -0.003-0.03, p = 0.83), nor for any of the individual radiological cSVD markers.

Conclusion: We found no association between the cSVD burden and PHE formation. This implies that mechanisms other than BBB dysfunction are involved in the pathophysiology of PHE.

Keywords: blood-brain barrier; intracerebral hemorrhage; magnetic resonance imaging; perihematomal edema; small vessel disease.