Brain involvement in Alström syndrome

Abstract

Background: Alström Syndrome (AS) is a rare ciliopathy characterized by cone-rod retinal dystrophy, sensorineural hearing loss, obesity, type 2 diabetes mellitus and cardiomyopathy. Most patients do not present with neurological issues and demonstrate normal intelligence, although delayed psychomotor development and psychiatric disorders have been reported. To date, brain Magnetic Resonance Imaging (MRI) abnormalities in AS have not been explored.

Methods: We investigated structural brain changes in 12 genetically proven AS patients (mean-age 22 years; range: 6-45, 6 females) and 19 matched healthy and positive controls (mean-age 23 years; range: 6-43; 12 females) using conventional MRI, Voxel-Based Morphometry (VBM) and Diffusion Tensor Imaging (DTI).

Results: 6/12 AS patients presented with brain abnormalities such as ventricular enlargement (4/12), periventricular white matter abnormalities (3/12) and lacune-like lesions (1/12); all patients older than 30 years had vascular-like lesions. VBM detected grey and white matter volume reduction in AS patients, especially in the posterior regions. DTI revealed significant fractional anisotropy decrease and radial diffusivity increase in the supratentorial white matter, also diffusely involving those regions that appeared normal on conventional imaging. On the contrary, axial and mean diffusivity did not differ from controls except in the fornix.

Conclusions: Brain involvement in Alström syndrome is not uncommon. Early vascular-like lesions, gray and white matter atrophy, mostly involving the posterior regions, and diffuse supratentorial white matter derangement suggest a role of cilia in endothelial cell and oligodendrocyte function.

Figure 1

Brain MRI: coronal T1-weighted (a) and axial FLAIR (b, c) images of Alström syndrome patients. a) 31-year-old male: mild brain atrophy with enlargement of ventricles and subarachnoid spaces; b) 11-year-old girl: enlargement of the left atrium of lateral ventricle; c) 18 year-old boy: bilateral dilated atria of the lateral ventricle.

Figure 2

Brain MRI of a 43-year-old male patient. Axial FLAIR (a, b); axial (c) and coronal (d) T1 weighted images. a,b) hyperintense rim bordering the margin of both lateral ventricles and a small lacune in the left head of the caudate (arrow); c, d) multiple small hypointense lesions in the cerebellar cortex.

Figure 3

TBSS and VBM analysis findings: colored areas show significant differences of Fractional Anisotropy, Radial Diffusivity, Axial Diffusivity, Mean Diffusivity, gray matter and white matter volume between Alström patients and controls. Diffuse myelin supratentorial involvement and regions of symmetric parenchymal atrophy.