Multimodal peripheral nervous system imaging to quantify, monitor, and understand the neuropathy of Friedreich ataxia

Damage to (1) peripheral sensory nerves in the limbs and (2) their cell bodies in the so-called dorsal root ganglia (DRG) just outside the spinal cord is a common finding in neuropathological studies of Friedreich ataxia (FA). Degeneration of both these structures contributes significantly to ataxia severity and, therefore, to a reduced quality of life. However, the exact mechanisms underlying peripheral nervous system (PNS) involvement in FA and its natural history remain incompletely understood. Combining (painless) ultrasound and MRI, Dr Maas and his collaborators propose the first longitudinal PNS imaging study in FA, which will include 20 patients and 20 healthy controls of comparable age and sex. In this project, they will use ultrasound to accurately measure the size of (1) nerve roots in the neck and (2) several nerves in the arms and legs at multiple sites. In addition, they will apply ultrahigh-frequency ultrasound at the wrist to evaluate individual fascicles of the median nerve with very high resolution. Third, this group will perform advanced MRI scans of the lower back to determine DRG volumes at different lumbar levels. All imaging data will be obtained at baseline and a 1-year follow-up visit, and complemented by a variety of clinician-reported and patient-reported outcomes to investigate the clinical meaningfulness of any imaging abnormalities. These will include, amongst others, ataxia severity, activities of daily living, fatigue, neuropathic pain, and quality of life. Finally, they will measure concentrations of neurofilament light chain in the blood, which reflects damage to large myelinated nerve fibers, and assess its relationship with ultrasound-measured nerve sizes and MRI-measured DRG volumes. Taken together, this proposal will (1) contribute to a better understanding and visualization of the sensory neuropathy in FA, (2) fill important knowledge gaps about the annual progression of PNS degeneration, and (3) hopefully yield imaging biomarkers of disease severity and progression that may be applied in future therapeutic trials.