Short-Term Frequently Relapsing Ischemic Strokes Followed by Rapidly Progressive Dementia in CADASIL

INTRODUCTION: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease with slow natural progression. Ischemic stroke and cognitive impairment are its most common clinical symptoms. Here, we report a rare 50-year-old woman who had rapid disease progression with c.457C>T, p.Argl53Cys heterozygous mutation in exon 4 of NOTCH3 and discuss the possible reasons. Furthermore, we summarized the clinical and neuroimaging characteristics of 14 CADASIL patients with Arg153Cys mutation in exon 4. CASE REPORT: The proband suffered acute ischemic stroke 5 times in 5 months, followed by rapidly progressive dementia (RPD) and inability to live independently, though she didn't have vascular risk factors and had been under standardized secondary prevention therapy since the first stroke. Magnetic resonance imaging showed extensive white matter hyperintensities, numerous ischemic infarcts and microbleeds, and severe brain atrophy. Her elder brother and other patients with Arg153Cys mutation in exon 4 all did not progress so quickly. Her multiple strokes may be associated with the poor self-regulation of vessels, which may promote the occurrence of RPD. Antiplatelet and anticoagulant drugs were difficult to prevent ischemic strokes. Severe imaging findings may indicate rapid progression of CADASIL. In addition, we found that headache was a very frequent symptom in CADASIL patients with Arg153Cys mutation in exon 4, accounting for 76.9%. CONCLUSIONS: CADASIL can also appear to have rapid progression, as illustrated by our proband, which is worthy of clinicians' attention and intervention timely. Headache may present in a relatively higher proportion of CADASIL patients with Arg153Cys mutation in exon 4.