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NEUROIMAGING MARKERS IDENTIFYING NOTCH3-MUTATION RELATED INTRACEREBRAL HEMORRHAGE
Abstract
Background and Aims
Hereditary cerebral small vessel disease (CSVD), such as NOTCH3-mutation, is an important differential diagnosis of spontaneous intracerebral hemorrhage (ICH). We aim to identify clinical and imaging characteristics discriminating NOTCH3-mutation related from non-genetic cause of ICH.
Methods
This study was based on a prospectively follow-up CSVD cohort. Next generation sequencing for the common genes of CSVD were performed in patients with ICH and suspicious hereditary cause, such as more severe features of CSVD or younger age of onset. Neuroimaging markers of CSVD, including white matter lesion (WML), lacunes, enlarged perivascular spaces, and cerebral microbleeds (CMB) were compared between patients with and without NOTCH3-mutation.
Results
From 445 patients who had received genetic screening, 47 NOTCH3-mutation and 68 non-genetic patients with ICH were enrolled. Compared with the non-genetic group, patients with NOTCH3-mutation were older, had higher frequency of family history of stroke, thalamus ICH, overwhelming more severe neuroimaging markers of CSVD, especially more CMB in the hippocampus (5.8+/-8.4 vs 0.3+/-0.6) and thalamus (8.4+/-8.2 vs 2.0+/-2.9, both P<0.001). Besides, patients with NOTCH3-mutation and higher risk of recurrent stroke (HR 2.42, 95% CI 1.13–5.20). We further constructed a NOTCH3-ICH score consisting of history of stroke in the siblings, severe deep WML, higher number of hippocampus CMB (>=2) and thalamus CMB (>=7). The sensitivity and specificity were 0.71 and 0.87 for a cut-off score of 2 points, and the area under the receiver operating characteristics was 0.85 (95% CI 0.77–0.93).
Conclusions
Patients with NOTCH3-mutation related ICH had higher burden of CMB in the hippocampus and thalamus. A NOTCH3-ICH score can be used to identifying potential genetic cause of CSVD.