Increased susceptibility and volume reduction in deep brain nuclei in primary orthostatic tremor

Background Primary orthostatic tremor (POT) is a rare progressive neurological disorder with a high-frequency tremor while standing. The pathophysiology remains uncertain, and imaging studies have been inconclusive.Objectives The primary objective was to assess whether neurodegenerative changes are detectable in POT by quantitative susceptibility mapping (QSM) on brain MRI. A second objective was to explore volumetric changes in subcortical grey matter and cerebellum.Methods In this cross-sectional study, 20 participants with POT and 14 age- and sex-matched healthy controls (HCs) were examined using a 3 T Siemens Prisma scanner with a T2*-weighted multiecho gradient-echo sequence for QSM. Regions of interest (ROIs) were automatically and manually segmented. Selected ROIs were the red nucleus, globus pallidus (GP), thalamus, caudatus, putamen, substantia nigra, dentate nucleus and inferior and superior colliculus.Results There was a significant increase in susceptibility in the red nucleus (mean susceptibility 138.1 parts per billion (ppb) in POT and 113.3 ppb in HC, p=0.015) and GP (mean susceptibility 101.2 ppb in POT and 73.3 ppb in HC, p=0.0015) and a significantly lower volume of the GP in the POT group compared with HC (mean volume 3838 mm 3 in POT and 4062 mm3 in HC, p=0.012).Conclusion Increased susceptibility and decrease of volume indicate the possibility of a neurodegenerative process affecting the red nucleus and GP in POT. The red nucleus and GP are involved in motor control, and a focal dysfunction in these networks may be a part of the cause of orthostatic tremor.