Differences between Spinocerebellar Ataxias and Multiple System Atrophy-Cerebellar Type on Proton Magnetic Resonance Spectroscopy
et al. (2012) Differences between Spinocerebellar Ataxias and Multiple System Atrophy-Cerebellar
Type on Proton Magnetic Resonance Spectroscopy. PLoS ONE 7(10): e47925. doi:10.1371/journal.pone.0047925
Differences between Spinocerebellar Ataxias and Multiple System Atrophy-Cerebellar Type on Proton Magnetic Resonance Spectroscopy
Jiing-Feng Lirng 0
Po-Shan Wang 0
Hung-Chieh Chen 0
Bing-Wen Soong 0
Wan Yuo Guo 0
Hsiu-Mei Wu 0
Cheng-Yen Chang 0
Thomas H. Gillingwater, University of Edinburgh, United Kingdom
0 1 National Yang-Ming University School of Medicine , Taipei, Taiwan , 2 Department of Radiology, Taipei Veterans General Hospital , Taipei, Taiwan , 3 Department of Neurology, National Yang-Ming University School of Medicine , Taipei, Taiwan , 4 Department of Medicine, Municipal Gandau Hospital , Taipei, Taiwan , 5 Department of Radiology, Taichung Veterans General Hospital , Taipei, Taiwan , 6 Department of Neurology, Taipei Veterans General Hospital , Taipei , Taiwan
Purpose: A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS) may help differentiate spinocerebellar ataxias (SCA) from multiple systemic atrophy- cerebellar type (MSA-C). Material and Methods: This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA) types 1, 2, 3, 6 and 17 (N = 94) and MSA-C (N = 62), and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. Results: When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p,0.002). The Cho/Cr was lower in SCA2 and MSA-C (p,0.0005). The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p,0.018). The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p,0.04). The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p,0.0005). In the early stages of diseases (SARA score,10), significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p,0.017). The Cho/Cr was lower in MSA-C or SCA2 (p,0.0005). Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p,0.016). Conclusion: By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C). Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.
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. These authors contributed equally to this work.
Cerebellar ataxias can be categorized into two groups:
hereditary or sporadic [1]. Sporadic cerebellar degeneration may
be the result of intoxication, endocrine disorders or idiopathic
causes, such as multiple system atrophy-cerebellar type (MSA-C).
Hereditary ataxias have different modes of inheritance with
mutations in scores of genes. Spinocerebellar ataxia (SCA)
represents the most common autosomal dominant cerebellar
ataxia and so far 36 distinct chromosomal loci have been
identified. They share similar manifestations, including ataxia,
pyramidal and extrapyramidal signs. The diagnosis of MSA-C can
only be reached when clinical and laboratory criteria are met in
accordance with the international consensus [2]. Patients with
MSA-C usually have a rapid clinical progression with a mean
survival of 69 years. An accurate diagnosis not only foretells the
prognosis, makes comprehensive genetic counseling possible, but
also helps design the best clinical management.
Atrophy and signal intensity changes in the cerebellum and
brain stem can be observed in both SCA and MSA-C using
magnetic resonance images. Although some characteristic features,
such as abnormal signal intensities in the middle cerebellar
peduncle, the hot cross bun sign and putaminal slit, may be
observed in patients with MSA [3], they usually are only
discernible in the late stages of the disease.
Creatine (Cr) measured in magnetic resonance spectroscopy
(MRS) is related to cell energy pathways and reflects the energy
potential available in the brain tissue. Its concentration in normal
brain remains very high (7.4960.12 mmol/kg) and stable and can
be used as a reference for comparisons. N-acetylaspartate (NAA) is
believed to be neuronal and axonal origin in adult brain [4,5] and
is a marker for neuronal integrity, density or volume [6,7]. A
reduction in NAA resonance has been observed in various
conditions associated with neuronal loss and/or axonal injury
[812]. Choline (Cho) resonance reflects total Cho stores, derived
from glycerophosphocholine and phosphocholine (...truncated)