Sarah-Luis Blendow

• Abstract Background and Purpose Fatigue is a symptom of many neurological diseases and is frequently a component of chronic pain disorders. Interestingly, inflammatory processes and central sensitization seem to play a role in both fatigue and chronic pain conditions, such as complex regional pain syndrome (CRPS). Yet, to date, there has been no systematic review of the prevalence and clinical presentation of fatigue and its impact on quality of life (QoL) in CRPS. This knowledge could help improvinge clinical care for this often difficult-to-treat condition. Methods In this prospective study, 181 patients with CRPS and a matched control group (n=141) were interviewed. In addition to clinical information, data on depression, fatigue and QoL were collected. Statistical analysis was performed between fatigue severity and CRPS severity, pain levels and clinical CRPS phenotype, as well as examination of the largest factors influencing QoL using best subsets regression. Results CRPS patients showed significantly higher fatigue levels compared to controls, indicated by higher FSMC scores (CRPS: 75 [57-85] vs. controls: 39 [25-57]). 85% experienced fatigue, with 6% mild, 15% moderate, and 67% severe. Severe fatigue was associated with higher pain intensities compared to no fatigue (rest: p = 0.003; movement: p = 0.007) or moderate fatigue (movement: p = 0.03). QoL in our cohort was mainly influenced by pain (movement: adj.R²=0.38; p<0.001, rest: Δadj.R² = 0.02, p=0.007) and depression (Δadj.R² = 0.12, p<0.001). Fatigue mediated the pain-depression relationship. Conclusions This pioneering study investigates fatigue prevalence, its relation to pain, and its impact on QoL in CRPS patients. Severe fatigue, closely tied to pain intensity, is prevalent. While pain and depressive symptoms predominantly affect QoL, fatigue may influence it indirectly by mediating the link between pain and depression. Regular fatigue assessment using standardized methods and clinical consideration are crucial in CRPS management.