Superior Cerebellar Peduncle Atrophy in Friedreich’s Ataxia Correlates with Disease Symptoms

Abstract

Friedreich's ataxia (FRDA) is the most common early onset inherited ataxia with clinical manifestations, including gradual progression of unremitting cerebellar-sensory ataxia, peripheral sensory loss, loss of lower limb tendon reflexes and hypertrophic cardiomyopathy. Although atrophy of the superior cerebellar peduncle (SCP) has been reported in several magnetic resonance imaging (MRI) studies of FRDA, the relationship of SCP changes to genetic and clinical features of FRDA has not been investigated. We acquired T1-weighted MRI scans in 12 right-handed individuals with FRDA, homozygous for a GAA expansion in intron 1 of FXN, as well as 13 healthy age-matched controls. The corrected cross-sectional areas of the right (left) SCP in the individuals with FRDA (R, 20 ± 7.9 mm(2); L, 25 ± 5.6 mm(2)) were significantly smaller than for controls (R, 68 ± 16 mm(2); L, 78 ± 17 mm(2)) (p < 0.001). The SCP volumes of individuals with FRDA were negatively correlated with Friedreich's ataxia rating scale score (r = -0.553) and disease duration (r = -0.541), and positively correlated with the age of onset (r = 0.548) (p < 0.05). These findings suggest that structural MR imaging of the SCP can provide a surrogate marker of disease severity in FRDA and support the potential role of structural MRI as a biomarker in the evaluation of neurodegenerative diseases and therapies.

Impact of cerebellar atrophy on cortical gray matter and cerebellar peduncles as assessed by voxel-based morphometry and high angular resolution diffusion imaging

“…However, other studies also failed to find significant correlations with cerebellar GM volume (Prakash et al, 2009;Akhlaghi et al, 2011) and found the ataxia score to be correlated with other metrics related to the cerebellar peduncles -dMRI metrics (Prakash et al, 2009) and volume metrics (Akhlaghi et al, 2011). This suggests that total cerebellar GM volume may not be the most sensitive marker of general ataxia score and a measure of the integrity of the cerebellar peduncles may be preferable, but only a very few studies have investigated correlation between ataxia score and dMRI metrics in cerebellar peduncles.…”

The Cerebellum Looks Normal in Friedreich Ataxia

“…1 However, the few reports mentioning cerebellar atrophy in FRDA were invariably based on subjective visual assessment of the cerebellar size or were focused on patients with late-onset FRDA, while morphometric assessment failed to show decreased cerebellar volume in patients with FRDA with typical disease onset before 25 years of age compared with agematched controls. 2 Lack of cortical cerebellar atrophy in FRDA was confirmed in a voxel-based morphometry study that, however, demonstrated volume loss of the deep peridentate WM. 3 Preservation of the cortex is in line with the pathologic descriptions of FRDA emphasizing that cerebellar damage involves the dentate nuclei and deep cerebellar WM.…”

“…4 A nonspecific finding emerging in FRDA is atrophy and microstrutural damage of the superior cerebellar peduncles that are correlated with disease duration and severity of the neurologic deficit. 2,3 Because the superior cerebellar peduncle contains most of the efferent fibers of the dentate nucleus, which is a site of primary neurodegeneration in FRDA, 4 the superior cerebellar peduncle alteration appears a promising biomarker for this disease but is not visually apparent and requires morphometry or computation of DTI measurements to be detected. Also, the increased magnetic susceptibility effects due to iron deposition observed in the cerebellar dentate nuclei of patients with FRDA require specific T2*acquisitions and postprocessing.…”

Determination of Genotypic and Phenotypic Characteristics of Friedreich’s Ataxia and Autosomal Dominant Spinocerebellar Ataxia Types 1, 2, 3, and 6

“…In addition, Akhlaghi et al (37) have demonstrated that superior cerebellar peduncle atrophy is correlated to onset age, disease duration, and weight of clinical findings. From neuroimaging, cerebellar atrophy and spinal atrophy were determined in 33.8% and 11.7% of our FA cases, respectively, while cerebellar atrophy was diagnosed in the two SCA6 cases but spinal atrophy was not observed.…”