Using Magnetic Resonance Imaging to investigate Glymphatic System alterations in Clinically Isolated Syndrome

Summary

Despite extensive research, chronic neurological diseases such as Multiple Sclerosis and Parkinson’s disease remain without a cure. The glymphatic system is a newly-discovered pathway the brain uses to get rid of waste products of metabolism. Evidences exist that failure of this system may underlie, or worsen pathology of neurodegenerative diseases, providing new avenues and targets for disease-modifying therapy. Early evidence suggests that inflammatory diseases, such as Multiple Sclerosis, may be linked to a glymphatic dysfunction.

What are we doing?

Our research studies people with a diagnosis of Clinically Isolated Syndrome, considered to represent the earliest clinical stage of Multiple Sclerosis. We are using an innovative imaging protocol constituted by a series of Magnetic Resonance Imaging sequences for the direct and indirect visualization of structural and functional changes related to a dysfunction of the glymphatic system.

The main aim of this research project is to determine if patients with Clinically Isolated Syndrome, often representing the initial manifestation of Multiple Sclerosis, show Magnetic Resonance Imaging evidence of alterations of the glymphatic system, compared with healthy volunteers.

How are we doing it?

Our cross-sectional research study will take place at the Exeter Clinical Research Facility and the Mireille Gillings Neuroimaging Centre. A group of 15 patients with a diagnosis of CIS and 15 healthy controls will undergo a screening clinical visit, with collection of clinical data and administration of scales and questionnaires, and collection of a blood sample for safety and disease-related biomarkers. An imaging visit where participants will undergo one MRI scan will collect imaging data about the structure and function of the brain related to the glymphatic system.

What happens next?

If the main objective is met, this project will provide first evidence that the glymphatic system is altered since the earliest detectable clinical stage of Multiple Sclerosis, that is, Clinically Isolated Syndrome.
Data obtained from this project will be used in a larger, longitudinal project in which the variables of glymphatic alteration that will emerge from the current study will be put in relationship with clinical progression (relapses of multiple sclerosis; the entity of the visible inflammation-related pathology in the brain (lesion load with Magnetic Resonance imaging and amount of activation of inflammatory cells with Positron Emission Tomography); and the degree of the patients’ response to their disease-modifying therapy. Ultimately, the aim is to individuate patients with Multiple Sclerosis in which a dysfunction of the glymphatic system could represent a major component of their pathology and which could benefit from tailored strategies of immunomodulatory intervention in future trials.