Exploring the relationships of physical, mental, and emotional symptoms and serum biomarkers of angiogenesis in multiple sclerosis.

Background: Multiple sclerosis (MS) involves symptoms that may be impacted by angiogenesis. Vascular endothelial growth factor (VEGF), a potent pro-angiogenic molecule, is elevated in early MS, but its activity in later disease is understudied. [Met⁵]-enkephalin (ENK) has anti-angiogenic activity and is decreased in persons with MS (PwMS).

Objectives: To determine salient symptoms of MS and evaluate relationships between common MS symptoms and angiogenesis-associated biomarkers.

Methods: PwMS and non-MS control participants were identified for this cross-sectional study. Walking times and self-reported fatigue, anxiety, depression, and pain were measured. Serum VEGF and [Met⁵] ENK levels were measured in a subset of PwMS.

Results: PwMS (n = 66) had significantly greater fatigue than controls (n = 35). In PwMS, fatigue, anxiety, depression, and pain were positively intercorrelated; fatigue was positively correlated with slower walking. Serum ENK and VEGF had a trending negative relationship. Serum ENK, but not VEGF, had a trending negative relationship with the length of disease. Serum ENK and VEGF were not correlated to walking time or self-report measures.

Conclusion: Fatigue is a salient MS symptom when compared to non-MS controls. Imbalanced pro- and anti-angiogenic signaling may influence fatigue in established MS, but further studies with larger sample sizes are needed to elucidate this potential relationship.