Genotype, Clinical Features and Imaging of Neuroradiological Abnormalities in CADASIL

Deepen the knowledge of the clinical phenotype CADASIL patient

Each patient with CADASIL will undergo to neuroimaging, correlating it with genotype (NOTCH3 gene mutation search outcome), clinical (e.g., the index event, cerebrovascular risk factors, associated manifestations) and instrumental (radiological) characterization.

Identify potentially reversible risk factors for disease progression

At baseline, each patient will undergo collection of demographic and clinical data (e.g., the index event, cerebrovascular risk factors, associated manifestations). Disability will be assessed with the modified Rankin Scale (mRS). Neuropsychological assessment will include administration of the Montreal Cognitive Assesment (MoCA) as a screening test. Some components of executive functions will be assessed by Frontal Assesment Battery (F.A.B) scale as a screening test of executive functions, Trail Making Test (TMT) A and B to assess visual search, psychomotor speed and selective attention (TMT test A) and in addition divided and alternating attention and cognitive flexibility by TMT test B, Attentional Matrices to assess sustained attention and visual search and Modified Five Point Test to assess spatial fluency. Finally by means of the Forward Word Span and Backward Digit Span, Verbal Short-Term Memory and Working Memory will be assessed. Alongside the neuropsychological assessment of

Identify clinical, genetic, biological and neuroradiological markers

Patients will undergo an MRI study with high-field (3T) equipment consisting of standard morphologic sequences (T1 3D TSE, T2 TSE, 3D FLAIR, SWI, DWI) to assess the extent of leukoencephalopathy, its distribution pattern, the presence of gaps and/or recent ischemic lesions in DWI sequences, perivascular spaces, and concomitant microhemorrhages. Laboratory approaches aimed at differentiating progenitors of specific cell populations (e.g., endothelial and vascular smooth muscle cells) from peripheral blood mononuclear cells (PBMCs) or fibroblasts from skin will be performed. In addition, it will be possible to isolate from peripheral blood the plasma component, intended for research and characterization of potential circulating biomarkers, by appropriate multi-omics approaches (transcriptomics, proteomics, lipidomics).

Deepen knowledge of the neuroradiological phenotype of CADASIL patients, depending on the NOTCH3 mutation locus identified (high, moderate or low risk)

Patients will undergo an MRI study with high-field (3T), in particular, high-resolution volumetric FLAIR sequences will be used to allow subsequent segmentation analyses of vascular lesions and a more correct quantitative assessment of cortical thickness values of brain areas. Advanced imaging sequences, particularly epi bold resting state for the study of functional brain connectivity, will also be provided.