ORIGINAL COMMUNICATION

Journal of Neurology

, Volume 253, Issue 4, pp 434-440

First online:

Diffuse structural and metabolic brain changes in Fabry disease

  • S. MarinoAffiliated withCentro Studi Neurolesi, Medical School University of MessinaNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
  • , W. BorsiniAffiliated withDepartment of Neurology and Psychiatry, University of Florence
  • , S. BuchnerAffiliated withDepartment of Neurology and Psychiatry, University of Florence
  • , M. MortillaAffiliated withDepartment of Radiology, Children Hospital Anna MeyerNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
  • , M. L. StromilloAffiliated withNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
  • , M. BattagliniAffiliated withNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
  • , A. GiorgioAffiliated withNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
  • , P. BramantiAffiliated withCentro Studi Neurolesi, Medical School University of Messina
  • , A. FedericoAffiliated withNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena
    • , N. De StefanoAffiliated withNeurology & Neurometabolic Unit, Dept. Neurological and Behavioral Sciences University of Siena

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Abstract

Objectives

To assess structural and metabolic brain changes in subjects affected by Fabry disease (FD) or carrying the disease mutation.

Background

FD is an X–linked metabolic disorder due to α-galactosidase A deficiency, which leads to storage of glycosphingolipids in many tissues and organs. Previous MR studies have shown structural and metabolic brain abnormalities in FD patients. It is not clear, however, whether tissue damage can be seen in both the brains of hemizygous and heterozygous and whether quantitative MR metrics are useful to monitor disease evolution.

Design/Methods

We studied 4 males and 4 females with FD. Each subject underwent brain proton MRI/MR spectroscopic imaging (MRSI) examinations to obtain measures of total brain volumes, total brain lesion volumes, magnetization transfer ratios (MTr) in WM and central brain levels of N–acetylaspartate (NAA) to creatine (Cr). A second MR examination was performed in five subjects after 2 years.

Results

Focal WM lesions were found in 2 males and 1 female. The MTr values were always low in the WM lesions of FD subjects (p < 0.001) and also were low in the normal–appearing WM of 2 affected males. Total brain volumes were never decreased in FD subjects. Brain NAA/Cr values were significantly (p = 0.005) lower in FD subjects than in normal controls and correlated closely with Rankin scale measures (r = –0.79). On follow–up examinations, no significant MR changes were found. However, the small changes in NAA/Cr correlated closely with changes in Rankin scores (r = –0.86).

Conclusions

Subtle structural and metabolic tissue damage can extend beyond WM lesions in FD subjects. Diffuse brain NAA/Cr decrease can be found in FD subjects in relation to the degree of their CNS involvement and its evolution over time.

Key words

magnetic resonance spectroscopy magnetization transfer brain atrophy Fabry disease