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Background and Purpose: The role of asymptomatic diffusion-weighted imaging-positive (aDWI+) lesions in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) patients remains unclear, and their radiographic features may differ from those of symptomatic diffusion-weighted imaging-positive (sDWI+) lesions. We aimed to investigate the clinicoradiographic characteristics of aDWI+ lesions in CADASIL patients., Methods: We conducted a retrospective analysis using data from the Taiwan CADASIL Registry. aDWI+ lesions were defined as incidentally detected DWI+ lesions without corresponding acute neurological deficits. We compared the baseline clinical characteristics of patients with and without aDWI+ lesions and analyzed their radiological features and evolution in relation to sDWI+ lesions., Results: Among 154 enrolled patients (mean age 62 ± 10 years), 17 (11%) had aDWI+ lesions. Baseline clinical characteristics were similar in the two groups, but those with aDWI+ lesions had more lacunes (median 8 vs. 2), multiple cerebral microbleeds (CMBs; 85% vs. 40%), and anterior temporal white matter hyperintensity (WMH; 47% vs. 14%). Multivariable analysis showed that aDWI+ lesions were associated with anterior temporal WMH (odds ratio 5.7, 95% confidence interval 1.5-21.0) after adjusting for multiple lacunes, multiple CMBs, and total WMH score. Compared to sDWI+ lesions, aDWI+ lesions were more often small infarcts (<1 cm; 89% vs. 23%) and less likely to involve the corticospinal tract (11% vs. 96%). Among the 11 aDWI+ lesions with follow-up magnetic resonance imaging, seven became microinfarcts, three became lacunes, and one disappeared., Conclusions: aDWI+ lesions in CADASIL are not uncommon and are associated with higher burdens of small vessel disease and anterior temporal WMH. Further research is needed to assess their long-term impact on CADASIL., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background and Purpose: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare inherited disease caused by NOTCH3 gene mutations. Although the main clinical features reflect brain injury, CADASIL is a systemic microangiopathy, and cardiac involvement has been observed but not systematically assessed. We aimed to study the prevalence and severity of coronary microvascular dysfunction (CMD) in CADASIL patients., Methods: Seventeen patients with genetically confirmed CADASIL, aged <60 years (mean age 40 ± 9 years), with ≤1 cardiovascular risk factor underwent neurological and neuropsychological evaluation, 3T brain magnetic resonance imaging (MRI), 12-lead electrocardiography (ECG), standard echocardiography, and measurement of myocardial blood flow at rest (resting MBF) and of maximal myocardial blood flow following Regadenoson infusion (Reg-MBF) by 13 NH 3 positron emission tomography (PET). Coronary flow reserve (CFR) was defined as Reg-MBF/resting MBF. PET results were compared to those of 15 healthy controls who were age and sex matched., Results: Twelve patients (71%) presented migraine, none (53%) had psychiatric disturbances, and one (6%) had a previous stroke. None had cognitive impairment or ECG or echocardiography abnormalities. Both Reg-MBF and CFR were blunted in CADASIL patients compared with controls (Reg-MBF 2.46 ± 0.54 vs. 3.09 ± 0.44 ml/g/min, respectively; p < 0.01; CFR 2.74 ± 0.36 vs. 3.28 ± 0.66, respectively, p < 0.01). No correlations were found between Reg-MBF values and neuropsychological performance or cerebral lesion burden on MRI., Conclusions: CADASIL patients exhibit blunted CFR due to CMD, which can be severe and is independent of the severity of brain lesion load and cognitive performances. CADASIL is a systemic microcirculation disease, and active surveillance of cardiac symptoms should be considered in these patients., (© 2020 European Academy of Neurology.)

Background and Purpose: Mutations in the NOTCH3 gene cause cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a cerebral small vessel disease manifesting with stroke, migraine and dementia in adults. The disease displays significant phenotypic variability that is incompletely explained. Early abnormalities in vascular function have been shown in animal models. We postulated that studying changes in vascular function may offer insights into disease progression., Methods: Twenty-two subjects with CADASIL [50% female, 50 (±11) years] from 19 pedigrees were included in a longitudinal multimodality study using brain magnetic resonance imaging (MRI), clinical measures, neuropsychology and measures of peripheral vascular function. MRI studies included measurement of structural brain changes, cerebral blood flow (CBF) and cerebrovascular reactivity by arterial spin labelling and a CO 2 respiratory challenge., Results: Over 2 years, new stroke or transient ischaemic attack (TIA) occurred in five (23%) subjects and new significant disability in one (5%). There were significant increases in number of lacunes, subcortical hyperintensity volume and microbleeds, and a decrease in brain volume. CBF declined by 3.2 (±4.5) ml/100 g/min over 2 years. CBF and carotid-femoral pulse wave velocity at baseline predicted change in subcortical hyperintensity volume at follow-up. Carotid intima-media thickness and age predicted brain atrophy. Baseline CBF was lower in subjects who showed a decline in attention and working memory., Conclusions: Cerebral blood flow predicts radiological progression of hyperintensities and thus is a potential biomarker of disease progression in CADASIL. Over 2 years, there were changes in several relevant imaging biomarkers (CBF, brain volume, lacunes, microbleeds and hyperintensity volume). Future studies in CADASIL should consider assessment of CBF as prognostic factor., (© 2020 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)