Clinical, familial, and neuroimaging features of CADASIL‐like patients. (11th August 2014)

• Record Type: Journal Article
• Authors: Nannucci, S.; Pescini, F.; Bertaccini, B.; Bianchi, S.; Ciolli, L.; Valenti, R.; Dotti, M. T.; Federico, A.; Inzitari, D.; Pantoni, L.
• Is Part Of: Acta neurologica Scandinavica. Volume 131:Number 1(2015:Jan.)
• Page Start: 30
• Page End: 36
• Publication Date: 2014-08-11
• Subjects: Neurology -- Periodicals; 616.8
• DOI: 10.1111/ane.12284
• Languages: English
• ISSNs: 0001-6314

Abstract

<abstract abstract-type="main" id="ane12284-abs-0001"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="ane12284-sec-0001" sec-type="section"> <title>Objectives</title> <p>Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is an inherited small vessel disease caused by <italic>NOTCH3</italic> mutations. There are no clinical and neuroimaging findings pathognomonic of the disease. The aim of this paper was to provide a description of a group of <italic>NOTCH3</italic>‐negative patients with a phenotype closely resembling that of CADASIL.</p> </sec> <sec id="ane12284-sec-0002" sec-type="section"> <title>Materials and methods</title> <p>We performed <italic>NOTCH3</italic> analysis (exons 2‐23) in 117 probands because of a clinician's suspicion of CADASIL. The CADASIL scale, a recently developed tool that allows to better select patients for <italic>NOTCH3</italic> analysis, was retrospectively applied to <italic>NOTCH3</italic>‐negative patients; the patient subgroup that scored higher than the screening cutoff for CADASIL was defined as CADASIL‐like.</p> </sec> <sec id="ane12284-sec-0003" sec-type="section"> <title>Results</title> <p>Thirty‐four CADASIL‐like patients (mean age at onset 57.8 years [52.1–63.4], 50% males) were identified. Compared with 25 patients with CADASIL for clinical, familial, and neuroimaging features, only the following variables were significantly (<italic>α</italic> level <0.05) different in frequency between patients with CADASIL and CADASIL‐like patients: a positive family history for stroke at age ≤60 years, more frequent in patients with CADASIL, and hypertension, more frequent in CADASIL‐like patients.</p> </sec> <sec id="ane12284-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Our experience highlights the growing number of patients presenting with a high suspicion of a cerebral small vessel disease with an autosomal dominant pattern of inheritance and a phenotype closely similar to that of CADASIL but without <italic>NOTCH3</italic> mutations. This group remains to be characterized from the genetic point of view. The role of other genes or <italic>NOTCH3</italic> alterations on exons other than 2‐23 or introns has to be further assessed.</p> </sec> </abstract>