Other Studies

Full Title: Progressive Degeneration from Onset in Pediatric Multiple Sclerosis: Evaluation of Clinical and Health-Related, Quality of Life, Early loss of Brain Integrity and Accelerated Immunological Senescence.

Multiple Sclerosis is a progressive disease with a burden that beings from the onset, including children diagnosed with the disease.

A recognized need exists to better understand the functional decline in physical and cognitive aspects of children and teens with MS and the ultimate impact on the quality of life of these individuals and their families. This comprehensive study aims to evaluate patient-relevant outcomes of pediatric-onset MS, using MRI metrics, biological samples and Health-Related Quality of life (HRQol)s questionnaires. The primary outcome is to compare HRQoL in both newly diagnosed, and long-standing MS patients entering adulthood, to healthy controls and pediatric patients with monophasic demyelination (single episode demyelinating event). We also aim to examine health care utilization by patients and their parents to fully understand the economic impact on health care systems. Using MRI metrics we assess the impact on brain integrity and maturation with a new focus on cortical pathology, and how brain tissue injury predicts HRQoL and cognition deficits. Using saliva and blood samples we examine the response of specific regulatory and effector immune cells in MS patients and the role Epstein Barr Virus (EBV) and vitamin D insufficiency play in immune imbalance. We conduct these assessments prospectively in our MS patients at 3,6,12 and 24 months to quantify the progressive burden of the disease clinically and radiologically. Finally, we evaluate the gut flora differences between MS, monophasic and age and sex-matched healthy controls, using stool samples collected at each visit.

One of the goals of our research is to understand the role of viral infections, in particular the Epstein Barr virus (EBV), in the development of multiple sclerosis (MS).

The cause of multiple sclerosis (MS) is still unclear but is likely to involve both genetic and environmental factors. EBV has consistently been shown to be associated with MS, and is recognized as one of the major environmental risk factors of MS. Almost all adult MS patients are infected with EBV and have high antibody levels against the virus before onset of neurologic symptoms. We have previously reported that in pediatric-onset MS patients, about 80-85% are infected with EBV, compared to only about 30-45% in age- and sex-matched healthy children. A history of infectious mononucleosis (IM), caused by EBV infection, also greatly increases the risk of developing MS.

EBV, also known as human herpesvirus 4, is a common human virus infecting > 90% adults worldwide. It is spread primarily through saliva. After initial infection, EBV stays in the body for life in a dormant (latent) state but will re-emerge once in a while to produce new viruses that are shed in the saliva. In healthy individuals, EBV infection is normally kept in tight control by the immune system. EBV reactivation is believed to play a significant role in the onset of MS as well as disease progression. In support of this hypothesis, we found that children with MS are more likely to shed EBV in the saliva (60-70% of the year) than healthy children (about 20% of the year), which suggests inadequate control of EBV infection. One of our current hypotheses is to further explore the biology of EBV infection and EBV-specific immune responses in paediatric-onset MS.