Clinical relevance of neuroimaging biomarkers of small vessel disease in relation to intracranial haemorrhage

Introduction: Determining the cause of spontaneous (non-traumatic) intracerebral haemorrhage (ICH) is critical to guide treatment and prognosis. We investigated whether small vessel disease (SVD) in addition to clinical and other radiological findings on acute neuroimaging predicts a low risk of a macrovascular cause (e.g. an arterio-venous malformation, aneurysm, or dural arteriovenous fistula). Patients and Methods: We identified patients with acute spontaneous ICH who underwent acute non-contrast CT, CT angiography (CTA) and intra-arterial digital subtraction angiography (IADSA) at our institution from January 2010-April 2014. Logistic regression including CTA result, SVD, age, pre-ICH hypertension and ICH location was used to derive a prediction model, validated using bootstrapping. Results: 173 patients (46% female, median age 49) of whom 78 had a macrovascular cause on IADSA were included. Predictors of a macrovascular cause were: abnormal CTA (OR 67.4; p<0.001); absence of SVD (OR 5.0; p=0.019); and absence of pre-ICH hypertension (OR 3.4; p=0.05). In our internally-derived prediction model, the combination of CTA, SVD and pre-ICH hypertension predicted the likelihood of an underlying macrovascular cause (optimism-adjusted ROC area 0.919). Patients with negative CTA, SVD and pre-ICH hypertension have a low likelihood of an underlying macrovascular cause (1.8%). Discussion and Conclusion: A combination of CTA, SVD and pre-ICH hypertension predict the likelihood of finding a macrovascular cause in patients with acute spontaneous ICH, allowing informed decisions regarding the likely benefit and risk of IADSA. Part 3: Intracerebral haemorrhage populations 98 6.1 Rationale for study Intracerebral haemorrhage (ICH) is devastating: mortality is 54% at 1 year (3), while only 12-39% of survivors recover to independence (4). Most cases (77–88%) of spontaneous (non-traumatic) intracerebral haemorrhage are termed “primary” (230), with a presumption that they are caused by small vessel disease (SVD) (33). However, it is critical to exclude “secondary” structural causes of ICH, including macrovascular causes (e.g. arterio-venous malformations, aneurysms, and dural arteriovenous fistulae), which can be treated. The “reference standard” for detection of a macrovascular cause is intra-arterial digital subtraction angiography (IADSA) or neurosurgery. IADSA is invasive, requires skilled operators and is associated with a small but appreciable mortality and morbidity, especially in acute ICH (12). Selecting which ICH patients have a sufficiently high likelihood of a macrovascular cause to recommend IADSA is a common and important clinical question. Current practice varies widely (13): typically, the presence of pre-ICH hypertension, deep location of ICH and age are used as indicators of SVD to select patients unlikely to require IADSA(13), but the evidence supporting this is scant and often conflicting (14-16). A scoring system developed in Boston incorporating pre-ICH hypertension and age (among other factors) to identify patients at risk of a macrovascular cause has been previously validated, but did not include neuroimaging markers of SVD and only had moderate discrimination outside of the United States. (231, 232). SVD can be directly identified on brain imaging by leukoaraiosis and lacunar infarction, even on plain CT. We therefore hypothesised that, in acute ICH patients, visualization of SVD will predict a low yield of a macrovascular cause; furthermore, we aimed to develop and internally validate an algorithm to help clinicians identify patients at high risk of having a macrovascular cause underlying acute