July 21, 2015
MS Scientific Research Foundation funded study boosts efforts in pediatric MS research, implications for understanding adult-onset MS
Before the launch of the Canadian Pediatric Demyelinating Disease Network in 2004, pediatric multiple sclerosis was under-recognized and poorly understood. The prevalence and impact of MS in children and adolescents was unknown, and how their MS differs from MS in adults was yet to be determined. The creation of a pan-Canadian clinical network of pediatric MS patients became a turning point in research and treatment of MS. Over the last 10 years, with support from the MS Scientific Research Foundation, the Canadian Pediatric Demyelinating Disease Network recruited over 430 children and adolescents from 23 sites across the country who presented with acute, demyelinating disease and observed them over time. Under the leadership of leading MS pediatric neurologist Dr. Brenda Banwell (The Hospital for Sick Children and The Children’s Hospital of Philadelphia), this work had profound impacts on how pediatric MS is understood and managed, and led to the creation of the Canadian Pediatric Demyelinating Disease database, which includes comprehensive biological and imaging data, and partnerships with researchers and clinicians around the world.
With support from a $3.2 million dollar grant from the MS Scientific Research Foundation, Dr. Banwell will continue to lead pediatric MS research efforts with co-investigators Dr. Ann Yeh (The Hospital for Sick Children), Dr. Amit Bar-Or (Montreal Neurological Institute, McGill University), Dr. Doug Arnold (Montreal Neurological Institute, McGill University), and Dr. Ruth Ann Marrie (University of Manitoba). Twenty Canadian pediatric sites in the Canadian Pediatric Demyelinating Disease Network will participate in this study, which will focus on the impact of MS on quality of life, health care service utilization, brain development, cognitive performance, and the immune system.
In their study, entitled, “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”, Dr. Banwell and colleagues will conduct research using the well-established national clinical pediatric MS network web database, and high-quality standard operating procedures for MRI and biological sample collection.
The aims of the study are to:
- Assess the burden of pediatric MS on physical and mental well-being, cognitive impairment, depression, anxiety and physical activity
- Evaluate patient and parental use of health care services, and determine the impact of modifiable risk factors such as level of physical activity
- Define the extent and progressive burden of pediatric MS using MRI, and assess the relationship of what is observed on MRI with patient-centered outcomes and immunological features
- Investigate immune imbalances in pediatric MS and determine how they relate to the extent of tissue integrity and disease.
The team will assess the impact of MS on health-related quality of life of pediatric patients using validated, reliable measures of physical functioning, emotional functioning, social functioning, and academic performance. They will also perform a one-hour, computerized cognitive test that assesses memory, reasoning, social cognition, and other executive brain functions. Additional questionnaires will be used to assess levels of depression and anxiety, and amount of physical activity.
They will use administrative data (physician visits, hospitalizations, ER visits etc.) to evaluate the use of health care services among pediatric patients and their parents. The team will employ advanced MRI techniques to link imaging cues to the biological, clinical and psychological outcomes observed in pediatric patients. MRI will also enable them to evaluate whether patterns of brain volume loss are associated with cognitive impairment.
Finally, the team will conduct biological experiments to identify different subsets of T cells and their activity levels in pediatric MS patients. They will also look at the aging process of immune cells to determine if there is “immune senescence” in children with MS. They will assess vitamin D levels and Epstein-Barr virus infection in pediatric patients and determine whether they are associated with immune abnormalities. They will obtain serum and DNA samples from the MS group and similar samples will be obtained from a healthy control group as a comparator.
Although much work has been done to raise awareness of, and better depict, pediatric MS, additional pertinent information is required to better understand the true impact of the disease. This multi-site and multi-disciplinary study has the capacity, through a well-established Canadian network of pediatric patients and experienced investigators, to address important needs and questions about pediatric MS that would otherwise be unattainable to study at a single centre. Additionally, understanding triggers, early neurodegenerative events, emotional and cognitive impacts, immune abnormalities, and MRI changes in the younger population affected by MS will advance our understanding of the time course of this disease, in turn leading to prompt initiation of neuroprotective strategies relevant for pediatric and adult-onset MS.