Exploring structural connectivity alterations in CRPS: Insights from diffusion imaging and clinical correlates

In recent years, functional and structural brain imaging studies have accumulated heterogeneous evidence for brain-wide changes accompanying complex regional pain syndrome (CRPS). We tested possible white matter pathologies in patients with CRPS in the chronic stage in comparison to matched healthy controls. We investigated possible alterations of structural connectivity using multi-directional diffusion-weighted imaging (MDDW) in a sample of 25 patients with unilateral upper limb CRPS and 19 matched controls. In a global approach we performed tract-based spatial statistics (TBSS) to evaluate possible structural differences between groups and/or association with clinical parameters (disease duration, pain intensity, CRPS severity score/CSS, somatosensory and motor function) for the patient group. In a hypothesis-driven approach (hypotheses were predefined in a trial), we tested differences between groups for fractional anisotropy (FA) in specific tracts (thalamus-M1/S1; accumbens-thalamus; anterior insula- PFC; corpus callosum between primary hand motor representations) and associations of FA and clinical parameters. We found no significant differences between patients and HCs for both approaches. However, when calculating associations between corpus callosal tract quantification and clinical parameters we detected decreased fractional anisotropy in association with disease persistence: the longer CRPS symptoms persisted, the lower callosal white matter quantification values between both M1 upper limb representations. Further studies have to address altered interhemispheric interaction with clinical features and the possible impact for new treatment strategies.