Kollmer and colleagues then sought to measure structural nerve abnormality markers in the sciatic and tibial nerves using magnetic resonance neurography (MRN). MRN is an imaging technique that focuses on visualizing nerves in your body using magnetic resonance imaging. In simple terms, it’s a way for doctors to see detailed images of your nerves. These images allow scientists to quantify how damaged a nerve may be by measuring its size and molecular composition. When used in the current study, all measures of size and composition were abnormal in SCA3 mutation carriers relative to control individuals, regardless of PN+ or PN- status. Moreover, the presentation of these abnormalities offers evidence that PN in SCA3 may be caused by a specific chronic degeneration of the cells and/or their associated nerve fibers that transmit signals between the body and the brain. This rules out the other possible cause of PN in SCA3, being demyelination of nerve fibers. In demyelination, the protective fatty sheath that insulates all nerve fibers to accelerate their electrical conduction progressively degenerates, causing nerve dysfunction and pain in the limbs. By providing evidence that nerve fiber- rather than myelin- degeneration is the more likely cause of PN in SCA3, the authors focus the ataxia field’s search for the underlying cause of PN to abnormalities in the nerve fibers themselves.

 Another interesting finding was that these structural abnormalities were found in pre-ataxic mutation carriers that did not exhibit functional nerve dysfunction in their electroneurographs. Although structural decay in this subset was not as severe as what was found in ataxic patients, this suggests that peripheral nerves may be affected by SCA3 before manifestation of motor ataxia symptoms and that there may be a threshold of nerve degeneration necessary to develop a clinically significant level of PN.

Finally, the authors identified potential markers for tracking structural abnormalities in SCA3 nerves – magnetization transfer ratio and proton spin density.  While slightly different from each other, both measures take advantage of the varying concentrations of protons in biological tissue to extract structural information from the nerve of interest. In this study, magnetization transfer ratio and proton spin density proved effective at differentiating PN+ SCA3 patients from PN- patients and pre-ataxic mutation carriers. This is an exciting finding as these measures may have some potential uses for tracking the progression of peripheral nerve degeneration in the future.