Brainstem Metabolites in Multiple System Atrophy of Cerebellar Type: 3.0-T Magnetic Resonance Spectroscopy Study
ABSTRACT The aim of this study was to find biomarkers of disease severity in multiple system atrophy of cerebellar type by imaging disease specific regions using proton magnetic resonance spectroscopy on a 3.0 T system.
We performed proton magnetic resonance spectroscopy separately in the pons and medulla on 12 multiple system atrophy of cerebellar type patients and 12 age and gender matched control subjects. The metabolite concentrations were estimated from single-voxel proton magnetic resonance spectra measured by point resolved spectroscopy, which were then correlated with clinical severity using Part I, II, and IV of the unified multiple system atrophy rating scale.
Proton magnetic resonance spectroscopy showed that myo-inositol concentrations in both the pons and medulla were significantly higher in multiple system atrophy of cerebellar type patients compared to those of the control subjects (P < 0.05). By contrast, total N-acetylaspartate (the sum of N-acetylaspartate and N-acetylaspartylglutamate) and total choline compounds concentrations in both the pons and medulla were significantly lower in multiple system atrophy of cerebellar type patients compared to control subjects (P < 0.05). Creatine concentration in the pons was significantly higher in multiple system atrophy of cerebellar type patients compared to the control subjects (P < 0.05). Furthermore, a significant correlation was found between the myo-inositol/creatine ratio in the pons and clinical severity, defined by the sum score of unified multiple system atrophy rating scale (I+II+IV) (r = 0.76, P < 0.01).
Proton magnetic resonance spectroscopy, in conjunction with a 3.0 T system, can be feasible to detect part of pathological changes in the brainstem, such as gliosis and neuronal cell loss, and the metabolites can be used as biomarkers of clinical severity in multiple system atrophy of cerebellar type patients.
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Article: Imaging in Multiple System Atrophy[Show abstract] [Hide abstract]
ABSTRACT: The diagnosis of multiple system atrophy (MSA) and its differentiation from Parkinson disease (PD) can be extremely challenging, particularly in early stages of disease. Both structural and functional imaging studies may be helpful for making the diagnosis, and may potentially be a means of monitoring disease progression. MRI may show distinctive patterns of atrophy and signal changes in MSA, such as the “hot-cross bun” sign and the hyperintense putaminal rim sign, which are relatively specific but have low sensitivity. Diffusivity may be particularly helpful in differentiating MSA from PD and appears to change over time, although the correlation with changes in motor dysfunction is uncertain. Diffusion weighted imaging can also reliably separate MSA from PSP by detecting alterations in the middle cerebellar peduncle. Volumetry can be used to detect characteristic patterns of atrophy. Alterations in spectroscopic patterns and abnormal iron deposition have also been reported. PET or SPECT measures of striatal dopamine innervations are abnormal in MSA and PD, addition of dopamine D2 receptor imaging (preserved in PD) may be helpful in differentiating the two. However, fluorodeoxyglucose (FDG) PET which show different characteristic metabolic networks in the two conditions that change with disease progression is probably more useful. Functional imaging can also be used to detect changes in cholinergic innervation in MSA, and to study neuroinflammation. Imaging of cardiac sympathetic innervation can also differentiate between PD and MSA and may be underutilized for this purpose.This article is protected by copyright. All rights reserved.08/2014; 2(6). DOI:10.1111/ncn3.125
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ABSTRACT: IntroductionPrevious magnetic resonance spectroscopy (MRS) and mass spectroscopy studies have shown accumulation of 2-hydroxyglutarate (2HG) in mutant isocitrate dehydrogenase (IDH) gliomas. IDH mutation is known to be a powerful positive prognostic marker in malignant gliomas. Hence, 2HG accumulation in gliomas was assumed to be a positive prognostic factor in gliomas, but this has not yet been proven. Here, we analyzed 52 patients harboring World Health Organization (WHO) grade II and III gliomas utilizing 3.0-tesla MRS.ResultsMutant IDH gliomas showed significantly higher accumulation of 2HG (median 5.077 vs. 0.000, p =0.0002, Mann¿Whitney test). 2HG was detectable in all mutant IDH gliomas, whereas in 10 out of 27 (37.0%) wild-type IDH gliomas, 2HG was below the detectable range (2HG =0) (p =0.0003, chi-squared test). Screening for IDH mutation by 2HG analysis was highly sensitive (cutoff 2HG =1.489 mM, sensitivity 100.0%, specificity 72.2%). Gliomas with high 2HG accumulation had better overall survival than gliomas with low 2HG accumulation (p =0.0401, Kaplan-Meier analysis).Discussion2HG accumulation detected by 3.0-tesla MRS not only correlates well with IDH status, but also positively correlates with survival in WHO grade II and III gliomas.11/2014; 2(1):158. DOI:10.1186/s40478-014-0158-y