Supratentorial atrophy in spinocerebellar ataxia type 2: MRI study of 20 patients

Abstract

There have been only few studies of brain magnetic resonance imaging (MRI) in spinocerebellar ataxia (SCA) type 2. We investigated 20 SCA2 patients, from 11 Sicilian families, and 20 age-matched control subjects using MRI. Our data confirm that olivopontocerebellar atrophy (OPCA) is the typical pattern in SCA2. We found no significant correlation between infratentorial atrophy, disease duration, or the number of CAG repeats in our SCA2 patients, but there was supratentorial atrophy in 12 patients, with a significant correlation between supratentorial atrophy and disease duration. OPCA appears to represent the "core" of the SCA2: however, central nervous system involvement is not limited to pontocerebellar structures. We therefore consider central nervous system degeneration in SCA2 as a widespread atrophy. MRI is helpful in diagnosing SCA, but it is not diagnostic in the absence of clinical and molecular studies. We suggest that serial MRI may play a role in evaluating "in vivo" the progressive steps of neurodegeneration in SCA2, for a better comprehension of the pathophysiology of this disorder.

Positive Selection of a Pre-expansion CAG Repeat of the Human SCA2 Gene

“…This study shows that the (CAG) 8 CAA(CAG) 4 CAA(CAG) 8 allele (a-5) of the CAG repeat in exon 1 of the SCA2 is significantly associated with a haplotype (CH-1) that has been detected to be under recent positive selection in CEU. As a result, a region of nearly one megabase of Chromosome 12 around this locus shows extensive LD.…”

“…We sequenced 130 bases (according to the reference genomic sequence) centered on CAG Figure 6. LD of CAG repeat in SCA2 gene with the 7 Adjacent SNPs (rs593226, rs616513, rs653178, rs695871, rs3809274, rs1544396, and rs9300319) Different alleles of CAG repeat were recoded as such: 1 ¼ (CAG) 8 repeat in SCA2 as described above. All the polymorphisms identified were in the CAG repeats, including the CAG copy number changes that were recoded as nucleotide polymorphisms.…”

“…The trinucleotide repeat expansion in this exon causes spinocerebellar ataxia [7], a neurodegenerative disorder typically with severe olivo-ponto-cerebellar atrophy [8,9], which affects the normal sensory/motor controlling functions. Previous studies of the triplet allele frequency distribution had shown that SCA2 was unusual, in that the pre-expansion allele accounted for more than 90% of sampled chromosomes [10], whereas much higher triplet polymorphism rates are commonly seen in other genes that underlie neurodegenerative diseases [11].…”

Adult-onset autosomal recessive ataxia with thalamic lesions in a Finnish family

“…34 Abnormal signal intensity of transverse pontine fibers has been reported in patients with SCA2 and other spinocerebellar ataxias. [35][36][37] High-intensity signals have been detected on T2-weighted images of the brainstem and thalamus, in addition to diffuse, high-intensity areas in cerebral white matter, in some patients with DRPLA. 38 MRI showed mild infratentorial atrophy and vague supratentorial atrophy.…”

Diffusion Tensor Imaging of Spinocerebellar Ataxias Types 1 and 2

“…The MR imaging correlates, namely atrophy and signal intensity abnormalities in the brain stem and cerebellum and supratentorial atrophy, can be assessed qualitatively, or with morphometric techniques. [10][11][12][13][14] They appear relatively late in progression of the disease and have poor correlation with clinical disability. 15 Mean diffusivity (also referred to as apparent diffusion coefficient, ADC) and fractional anisotropy (FA) from diffusion tensor imaging (DTI) have gained widespread acceptance as sensitive indicators to quantify microstructural damage of gray and white matter in neurodegenerative diseases.…”