James Nicholas Brenton, M.D., is the director of the University of Virginia’s Pediatric and Young Adult MS and Related Disorders Clinic. He is also associate professor of neurology and pediatrics for clinical research and performs collaborative clinical research within the field of pediatric MS. His research focuses on pediatric demyelinating disease and autoimmune epilepsies.
As the director of a clinic focusing on pediatric and young adults MS and related disorders, how do modifiable risk factors such as obesity, smoking, et cetera, increase the risk of MS in general?
Dr. Brenton: There are several risk factors for pediatric-onset MS. When I say pediatric-onset, I'm referring to patients with clinical onset of MS prior to the age of 18 years. Some MS risk factors are not considered “modifiable,” such as genetic risks. The greatest genetic risk for MS is related to specific haplotypes in the HLA-DRB1 gene. Another risk factor that is less amenable to modification is early exposure to certain viruses, like the Epstein-Barr virus (Makhani, et al 2016).
On the other hand, there are several potentially modifiable risk factors for MS. This includes smoking - either first or second-hand smoke. In the case of pediatric MS patients, it is most often related to second-hand (or passive) smoke exposure (Lavery, et al 2019). Another example of a modifiable MS risk factor is vitamin D deficiency. Vitamin D levels are influenced significantly by duration and intensity of direct exposure to sunlight, which depends (in part) on the geographic location of where you grow up. For example, those who live at higher latitudes (e.g. live further away from the equator) have less exposure to direct sunlight than a child who lives at lower latitudes (e.g. closer to the equator) (Banwell, et al 2011).
Obesity during childhood or adolescence is another modifiable risk factor for MS. Obesity’s risk for MS (like smoking) is dose-dependent – meaning, the more obese that you are, the higher your overall risk for future development of MS. In fact, the BMI in children with MS is markedly higher than their non-MS peers, and begins in early childhood, years before the clinical onset of the disease (Brenton, et al 2019).
There is mixed evidence regarding the impact of certain perinatal factors on future risk for MS. For example, some literature suggests that Caesarean delivery increases the risk of MS (Maghzi, et al 2012). Our research has found that infantile breastfeeding is associated with a lower future risk of pediatric-onset MS (Brenton, et al 2017).
Children are two to three times more likely to experience MS relapses compared with adults. How likely is it for the childhood obesity epidemic to lead to increased morbidity from MS or CIS, particularly in adolescent girls?
Dr. Brenton: Obesity is a systemic disease that manifests as excessive or abnormal accumulation of body fat. We know that chronic obesity leads to higher overall morbidity, lower quality of life, and reduced life expectancy. There are several common co-morbidities associated with obesity - like cardiovascular disease, type II diabetes mellitus, hypertension, polycystic ovarian syndrome, dyslipidemia, infertility, and some cancers (Abdelaal, et al 2017). Certainly, all these implications for the general population would pertain to those with MS who exhibit chronic obesity.
While we have fairly good evidence that obesity is a causal risk factor for the development of MS, there actually is a paucity of literature that has studied the impact of persistent obesity on an already established MS disease state. Several recent studies show that obesity is associated with a pro-inflammatory state in the blood and cerebrospinal fluid of MS patients (Stampanoni, et al 2019). There are other studies that shown a direct association between MS-related neurologic disability and obesity – such that those with a greater waist circumference exhibit higher rates of neurologic disability (Fitzgerald, et al 2019).
Recent studies have assessed whether SNAP factors are associated with health outcomes. How does a modifiable SNAP risk score in people with multiple sclerosis impacts the likelihood of disability worsening??
Dr. Brenton: SNAP factors may not be as well known to some people in this field. SNAP factors refer to smoking (“S”), poor nutrition (“N”), alcohol consumption (“A”) and insufficient physical activity (“P”). These four factors appear to be the most preventable causes of morbidity within the general population. SNAP factors are common in people with MS. The most common SNAP factors in MS patients are poor nutrition and insufficient physical activity. Cross-sectionally, these factors appear to be associated with worsening neurologic disability (Marck, et al 2019).
There is data suggesting that SNAP factors, particularly those that increase over time, can associate with worsening disability when followed over several years. Importantly, your baseline SNAP score does not appear to predict your future level of disability (Marck, et al 2019). Collective SNAP scores have not yet been well-studied in pediatric MS patients, but are important to study - particularly given that children with MS reach maximum neurologic disability at a younger age than adult-onset MS patients (Renoux, et al 2007).
What are some of the best practices MS health care providers can engage in to promote exercise and rehabilitative protocols to significantly impact the physical and cognitive performance of MS patients?
Dr. Brenton: Even though pediatric MS patients exhibit relatively low levels of physical neurologic disability early in their disease, the physical activity levels of youth with MS are quite low. These patients engage in less moderate and vigorous physical activity when you compare them to their non-MS peers (Grover, et al 2016), but we still don't fully understand why this is the case. In fact, it may be related to several different factors - including pain, fatigue, sleep quality, MS disease activity, and psychological factors (such as depression, social anxiety, and perceptions of self-efficacy). In order to truly provide patient-specific interventions that positively impact physical activity we need to better understand what factors to study and how these factors play into the individual patient. For example, if high levels of fatigue are inhibiting a patient from being physically active, the provider should explore sources of fatigue: “how are sleep patterns?”, “are they napping throughout the day?”, “does the fatigue occur only after a period of physical activity, or is it persistent despite how active they are?” These are examples of questions that may lead a neurologist to different approaches for managing reduced physical activity.
Generally speaking however, pediatric and adult MS providers would ideally provide healthy nutrition guidance and counseling to all patients, regardless of their weight. Though there is no particular proven “MS diet,” in general, we recommend a balanced diet that is lower in saturated fats and processed sugars and higher in fruits and vegetables. In the case of a pediatric MS patient, it's important to have the family on board with consuming a healthier diet, as parental involvement increases the likelihood of healthy behavioral changes in the child.
It is important to ask patients targeted questions about their physical activity and assist with goal setting toward achievable targets. If the patient is receptive, a provider can advise on the use of digital interventions, like apps or internet-based social groups that incorporate education, accountability, and self-monitoring. What we do not know yet, but hope to know soon, is if physical activity and/or reducing obesity/improving diet can serve as a modifier of disease in kids and adults with MS. My current research is focused on studying the role of obesity and diet on the clinical course of children with MS. Many others are studying the role of physical activity on the disease course of children with MS. Suffice to say, there is much more to learn on the role of diet, body composition, and physical activity in youth with MS.