Stroke: Highlights of Selected Articles

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is characterized by migraine, frequently with aura, transient ischemic attacks and strokes, mood disorders, and cognitive decline leading progressively to dementia and disability in the setting of suggestive neuroimaging. Given the variable expression of these parameters among individuals, definitive diagnosis is established by sequencing the whole NOTCH3 gene from a blood sample. The less expensive approach to assess for mutations in smalland medium-sized arteries skin biopsy sample is specific but with variable sensitivity. Pescini and colleagues sought to develop a clinical screen to predict the genetic diagnosis of CADASIL to select patients with a high probability to be affected by the disease and the need for genetic testing. First, they performed a pooled analysis of 15 published CADASIL series to derive a preliminary CADASIL scale. Second, they applied this preliminary scale to patients with genetically established CADASIL (n=61) and NOTCH3-negative patients with a phenotype similar to CADASIL (n=54) that were followed in the authors’ centers. Notably, only data available at the time of disease suspicion, that is, when genetic testing would be considered, were used. Receiver operating characteristic analysis was then performed to identify a cut-off point able to predict the presence of the disease. Third, logistic regression analyses including a third group of patients with small vessel disease (and the variable age at first transient ischemic attack or stroke) were performed to develop the definite CADASIL scale that included weighted scores for clinical, neuroimaging, and family history parameters. Finally, ad-hoc optimization of the cut-off point was developed. On the basis of this scale (score ranging from 0 to 25), patients scoring ≥15 points should undergo genetic analysis. As the authors point out, this scale will require confirmation and potential further optimization. Despite its limitations, this scale represents a simple screening tool that may aid the nonexpert in his decision making by asking the right questions. See p 2871.