Modifications of brain tissue volumes in facioscapulohumeral dystrophy
Introduction
Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant neuromuscular disorder characterized by progressive weakness of muscles in the face, shoulder girdle and upper arm.
Several evidences suggest the possibility of CNS involvement in FSHD. The FSHD Region Gene 1, one of the candidate genes for FSHD, is transcribed in human brain cells (van Deutekom et al., 1996), and FSHD can be rarely associated to CNS disorders, including central auditory function with sensorineural hearing loss (Brouwer et al., 1991, Fierro et al., 1997) (although in association with a D4Z4 repeat size of 10–11 kB, and mainly in early onset FSHD (Rogers et al., 2002)), schizophrenia (Sharma and Namrata, 2004), epilepsy and mental retardation (Funakoshi et al., 1998, Miura et al., 1998) (in childhood FSHD with larger gene deletion in the FSHD gene region).
Furthermore, previous studies have reported a relatively high incidence of WM hyperintensities in FSHD patients (Fierro et al., 1997), and a sporadic association with multiple sclerosis has been reported (Mishra et al., 1984).
Finally, a functional evaluation of CNS by transcranial magnetic stimulation has shown significantly less intracortical inhibition in FSHD patients as compared to normal subjects (NS) as well as to patients with other muscle diseases (Di Lazzaro et al., 2004).
However, to the best of our knowledge, no structural study of the brain has been carried out in FSHD patients.
Aim of our study was to compare the volumes of brain tissues, as measured by segmentation of MRI studies, in patients with FSHD versus a group of NS.
The effect of the disease onto global volumes of gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) was assessed by multiple regression analysis, taking into account head size, age and sex. In addition, voxel-based morphometry (VBM (Ashburner and Friston, 2000)) was used to compare regionally GM volumes between the two groups.
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Patient population
Thirty patients with FSHD (11 female) were included in the study. FSHD diagnosis was established based on clinical findings and by restriction fragment polymorphism analysis performed on genomic DNA by means of two restriction enzymes (EcoRI and BlnI), hybridized with the probe p13E-11 (D4F104S1).
FSHD patients included 18 hereditary cases (belonging to 12 families) and 12 apparently sporadic cases. The mean age of the patient group was 43.6 ± 14.3 years (age range 20–72), with a mean age of
Results
At visual inspection, four patients (two female, age range 20–46, three hereditary) presented focal WM hyperintensities (WMH) in T2w images (Fig. 1).
In three cases, WMH were mild and mostly periventricular and were associated with only minimal hypointensity in the corresponding T1w images, while in the third one (male, hereditary FSHD), there were rounded marked T2w hyperintensities in the centra semiovalia and periventricular supratentorial WM, corresponding to low-intensity areas in PDw and
Discussion
To the best of our knowledge, this is the first study to demonstrate GM loss in the brain of patients with FSHD. This was achieved using an operator-independent segmentation technique, thus avoiding possible operator errors or bias.
At VBM, GM loss appeared to be mainly located in the left frontal lobe, with smaller clusters of GM loss in the anterior cingulate and right fronto-polar cortex.
Localized GM loss suggests that brain atrophy in these patients is not due to global changes resulting
Conclusion
We have demonstrated a structural involvement of the brain in FSHD. To the best of our knowledge, this is the first study to demonstrate the presence of GM volume reduction in this pathology, thus adding to the spectrum of the disease.
Further work is needed to assess the role of these alterations in the clinical phenotype of this pathology, as well as to clarify in this respect the role of WMH.
Comparison with other myopathy groups is also warranted to exclude the occurrence of a nonspecific
Acknowledgments
Part of this work has been carried out within PVEOut, an EC cofinanced R and TD project (5th Framework Programme, contract QLG3-CT2000-594).
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