<h4>INTRODUCTION: </h4><br>Aim of this study is to elucidate possible <br>mechanisms of extrapyramidal damage in Fabry Disease (FD), a condition <br>in which involvement of the motor system has been recently suggested, by<br> simultaneously assessing morphometric and susceptibility changes of <br>striatonigral pathway and their possible correlations with clinical <br>variables.<br><h4>METHODS: </h4><br>In this cross-sectional study, we <br>investigated possible differences in terms of Quantitative <br>Susceptibility Mapping (QSM) values and volumes of different <br>extrapyramidal relays, including striatum and substantia nigra (SN), in <br>30 FD patients (M/F = 11/19, mean age 42.6 ± 12.2) and 37 healthy <br>controls (HC) (M/F = 16/21, mean age 43.2 ± 14.6). Patients underwent a <br>clinical examination for the study of different motor functions, and the<br> relationship between MRI and clinical variables was tested using the <br>Spearman's coefficient.<br><h4>RESULTS: </h4><br>Compared to HC, FD <br>patients showed an increase in susceptibility values of the SN <br>(p < 0.001) and striatum (p = 0.001), while no difference emerged for<br> the other tested extrapyramidal structures, suggesting their relative <br>sparing. The increased susceptibility was coupled to a reduced volume of<br> the SN (p < 0.001), but not of the striatum (p = 0.34). Finally, no <br>significant correlation emerged when probing the relationship between <br>these modifications and the clinical variables.<br><h4>CONCLUSION: </h4><br>In<br> FD patients, susceptibility and volumetric alterations are present <br>throughout the extrapyramidal pathway, with the SN being particularly <br>affected by these changes. Such results are in line with the subtle <br>extrapyramidal involvement recently suggested in FD, and could further <br>contribute to the understanding of the physiopathological bases of <br>cerebral involvement in FD.<br>