White matter microstructural alterations in patients with persistent headache after COVID-19 infection: an exploratory study

Objective: To evaluate white matter alterations in patients with persistent headache after COVID-19 resolution.
Methods: Exploratory case-control study. Highresolution brain diffusion Magnetic Resonance Imaging data were acquired in patients with persistent headache after COVID-19 infection and healthy controls (HC). Tract-Based Spatial Statistics was used to compare fractional anisotropy (FA), axial diffusivity (AD), mean diffusivity (MD), radial diffusivity (RD) and the return-to-axial (RTAP), return-to-origin (RTOP) and return-to-plane probability (RTPP) between the groups. RTAP, RTOP and RTPP were obtained with a new approach called AMURA (https://www.lpi.tel.uva.es/AMURA). Significant results were considered with p < 0.05 (Family-Wise Error corrected) and region size larger than 30 mm3.
Results: Ten patients with persistent headache after COVID-19 (mean age: 53.8 +- 7.8 years; nine women) and 10 HC balanced for age and sex (mean age: 53.1 +- 7.0 years; nine women) were included in the study. Significant higher AD and lower RTPP values were found in patients with persistent headache compared to HC in five regions from the corona radiata, and the external and internal capsule. In the patients, significant lower RTPP values were identified in six additional areas from the same tracts and the superior longitudinal fasciculus. No additional changes were found.
Conclusions: White matter axonal alterations are present in patients with persistent headache after COVID-19 infection.