Clinical neuroimaging in intracerebral haemorrhage related to cerebral small vessel disease: contemporary practice and emerging concepts

ABSTRACT

Introduction

About 80% of all non-traumatic intracerebral hemorrhage (ICH) are caused by the sporadic cerebral small vessel diseases deep perforator arteriopathy (DPA, also termed hypertensive arteriopathy or arteriolosclerosis) and cerebral amyloid angiopathy (CAA), though these frequently co-exist in older people. Contemporary neuroimaging (MRI and CT) detects an increasing spectrum of hemorrhagic and non-hemorrhagic imaging biomarkers of small vessel disease which may identify the underlying arteriopathies.

Areas covered

We discuss biomarkers for cerebral small vessel disease subtypes in ICH, and explore their implications for clinical practice and research.

Expert opinion

ICH is not a single disease, but results from a defined range of vascular pathologies with important implications for prognosis and treatment. The terms ‘primary’ and ‘hypertensive’ ICH are poorly defined and should be avoided, as they encourage incomplete investigation and classification. Imaging-based criteria for CAA will show improved diagnostic accuracy, but specific imaging biomarkers of DPA are needed. Ultra-high-field 7 T-MRI using structural and quantitative MRI may provide further insights into mechanisms and pathophysiology of small vessel disease. We expect neuroimaging biomarkers and classifications to allow personalized treatments (e.g. antithrombotic drugs) in clinical practice and to improve patient selection and monitoring in trials of targeted therapies directed at the underlying arteriopathies.

KEYWORDS:

• Intracerebral hemorrhage
• small vessel diseases
• cerebral amyloid angiopathy
• deep perforator arteriopathy
• hereditary small vessel disease
• amyloid-related inflammation
• neuroimaging
• MRI
• CT
• emerging strategies

Article highlights

• As a first step in intracerebral hemorrhage (ICH) investigation, treatable causes, such as macrovascular bleeding sources should be sought. Age, lobar or posterior fossa hemorrhage location (versus deep ICH), absence of small vessel disease and abnormal vessels on CT angiography independently predict a higher probability of an underlying macrovascular cause¹.

• The majority of ICH is due to sporadic small vessel diseases (SVD), namely deep perforator arteriolopathy (DPA) and cerebral amyloid angiopathy (CAA). DPA mainly affects mainly small arteries and arterioles in the basal ganglia, thalami, brainstem, deep cerebellar nuclei, and white matter (medullary) perforators², while CAA affects leptomeningeal and superficial cortical vessels³.

• MRI is the gold-standard for the non-invasive diagnosis of SVD. Presence, distribution, and severity of SVD markers (cerebral microbleeds, cortical superficial siderosis, white matter hyperintensities, lacunes, enlarged perivascular spaces) are associated with the underlying type and severity of the SVD and can help to predict ICH recurrence [67, 80, 84, 85, 91, 95, 98, 99, 105].

• Non-invasive diagnostic criteria for CAA allow the diagnosis of probable CAA even in the absence of supporting pathology. The Boston criteria include the presence of multiple lobar hemorrhagic manifestations (macro- and microbleeds, cSS) on MRI or CT and no concurrent cause for ICH⁴, while the Edinburgh CT criteria require lobar hemorrhage with subarachnoid extension and/or finger-like projections in patients with at least one APOE ɛ4 allele⁵. No comparable criteria exist for DPA. Non-hemorrhagic MRI markers (e.g. enlarged perivascular spaces) also show promise as biomarkers of the type of underlying arteriopathy.

• CSF biomarkers including Aβ-40, Aβ-42 and others might be a promising marker to incorporate in future diagnostic studies and criteria for CAA. The differences in biomarker patterns for Aβ-40 and Aβ-42 in comparison to Alzheimer’s disease presumably reflect specific differences in the pathophysiology of these amyloidopathies [115,116].

• Advanced and ultra high-field MRI might improve the detection, precise localization and characterization of previously underestimated SVD markers, and contribute toward a profound understanding of SVD.

Funding

This paper was not funded.

Declaration of interest

MG: none related to the paper; research funding by Bangerter-Rhyner Foundation and Swiss Stroke Society and grants from the European Stroke Organisation, Mittelbauvereinigung der Unviersität Bern and Pfizer (congress grant) outside the submitted work. DJS: none related to the paper; research funding by Swiss National Science Foundation, Swiss Heart Foundation, Bangerter-Rhyner Foundation, Swiss Society of Neurology and Bayer Foundation. Advisory board for Bayer and Portola/Alexion. DJW: none related to the paper; research funding from the British Hearth Foundation and the Stroke Association. Advisory boards for Portola, NovoNordisk, Bayer; and lectures for Bayer. All other authors have nothing to disclose. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosure

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.