Reduced Intracranial Volume in Fabry Disease: Evidence of Abnormal Neurodevelopment?

Giuseppe Pontillo, Sirio Cocozza, Arturo Brunetti, Vincenzo Brescia Morra, Eleonora Riccio, Camilla Russo, Francesco Saccà, Enrico Tedeschi, Antonio Pisani, Mario Quarantelli

Introduction: Lysosomal storage disorders (LSD) are often characterized by abnormal brain development, reflected by a reduction of intracranial volume (ICV). The aim of our study was to perform a volumetric analysis of intracranial tissues in Fabry Disease (FD), investigating possible reductions of ICV as a potential expression of abnormal brain development in this condition. Materials and Methods: Forty-two FD patients (15 males, mean age 43.3 ± 13.0 years) were enrolled along with 38 healthy controls (HC) of comparable age and sex. Volumetric MRI data were segmented using SPM12 to obtain intracranial tissue volumes, from which ICV values were derived. Results: Mean ICV of FD patients was 8.1% smaller compared to the control group (p < 5·10-5). Unlike what typically happens in neurodegenerative disorders, no significant differences emerged when comparing between the two groups the fractional volumes of gray matter, white matter and CSF (i.e., normalized by ICV), consistent with a harmonious volumetric reduction of intracranial structures. Discussion: The present results suggest that in FD patients an abnormality of brain development is present, expanding the current knowledge about central nervous system involvement in FD, further emphasizing the importance of an early diagnosis.