Study of the glymphatic system in small vessel disease

The glymphatic system is a cerebral waste clearing pathway occurring mainly through the perivascular space (PVS) network that seems to be involved in several neurological disorders, including small vessel disease (SVD) and sleep disorders. We aim to assess the function of the glymphatic system in relation to the grade of PVS enlargement and the quality of sleep in patients with lacunar stroke. We will enrol 50 consecutive patients with a lacunar stroke from the two centres of Barcelona (Hospital Clínic and Sagrat Cor) for 8 months. The study visit will be scheduled from 4 to 8 weeks after the index stroke and will include neurological evaluation and sleep quality scales (Pittsburgh Sleep Quality Index and Epworth Sleepiness Scale). The enrolled patients will undergo 3-T advanced investigational MRI at +/- 7 days from the study visit to evaluate the load of SVD markers, including the burden of enlarged PVS, and to assess the function of the glymphatic system by a measure derived from Diffusion Tensor Imaging (DTI) estimating the flow dynamics along the perivascular spaces (DTI-ALPS index). The MRI analysis will include a visual evaluation of the number of lacunes, microbleeds, a score for the perivascular spaces load in basal ganglia and centrum semiovale and white matter hyperintensity (WMH) (Fazekas score). The quantitative MRI assessment will include WMH volume, EPVS volume, brain volume, and DTI-ALPS index. Using Spearman correlation, we will analyse the simple associations between the main variables (PVS load and volume, DTI-ALPS index, and sleep quality scales). Multivariable linear or ordinal regression models depending on the characteristics of the dependent variable, will include pre-specified variables associated with stroke and SVD.