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Association between proton magnetic resonance spectroscopy measurements and CAG repeat number in patients with spinocerebellar ataxias 2, 3, or 6.

Wang PS, Chen HC, Wu HM, Lirng JF, Wu YT, Soong BW - PLoS ONE (2012)

Bottom Line: Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects.The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression.These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

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Representative cerebellar proton magnetic resonance (MR) spectra.(A) (Upper left) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper right) plane of the vermis in a normal subject at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (creatine [Cr]), red arrow (N-acetyl aspartate [NAA]), blue arrow (choline [Cho]), and yellow arrow (myoinositol [MI]). (B) (upper left) plane of the left hemisphere in a patient with spinocerebellar ataxia (SCA) at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a patient with SCA at which the MRS signal was acquired; (upper right) plane of the vermis in a patient with SCA at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (Cr), red arrow (NAA), blue arrow (Cho), and yellow arrow (MI).
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pone-0047479-g001: Representative cerebellar proton magnetic resonance (MR) spectra.(A) (Upper left) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper right) plane of the vermis in a normal subject at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (creatine [Cr]), red arrow (N-acetyl aspartate [NAA]), blue arrow (choline [Cho]), and yellow arrow (myoinositol [MI]). (B) (upper left) plane of the left hemisphere in a patient with spinocerebellar ataxia (SCA) at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a patient with SCA at which the MRS signal was acquired; (upper right) plane of the vermis in a patient with SCA at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (Cr), red arrow (NAA), blue arrow (Cho), and yellow arrow (MI).

Mentions: Brain MRI and MRS were performed with a 1.5-T system (Signa EXCITE, GE Medical Systems, Milwaukee, WI, USA). The MRI protocol consisted of an axial, T1-weighted, three-dimensional, fast-spoiled, gradient-recalled acquisition of steady-state images (TR 8.58 msec, TE 3.62 msec, inversion time [TI] 400 msec, slice thickness 1.5 mm) and an axial, T2-weighted, fast spin-echo sequence (TR 4000 msec, TE 256.5 msec, slice thickness 5 mm). After MRI, proton MRS of the bilateral cerebellar hemispheres and the cerebellar vermis was performed with a single-voxel, stimulated echo-acquisition mode sequence (Fig. 1, TR/TE/mixing time/excitations: 3000/15/13.7/96; spectral width  = 2500 Hz, number of points  = 2048, voxel size  = 1.8±2 cm×2 cm ×2 cm). The voxel of interest (VOI) for each subject was selected so as to correspond to the anatomy of the region being investigated (cerebellar hemispheres and vermis) and was performed by the same investigator (JFL) to ensure consistent placement. Individual VOIs were confirmed by two additional investigators (HCC, HMW) from three-dimensional maps overlaid on T2-weighted images for further processing. Measurements were derived by the software associated with the MRI equipment. Care was taken to avoid cerebrospinal fluid–filled spaces within the VOIs. Peak areas for NAA at 2.02 parts per million (ppm), creatine (Cr) at 3.03 ppm, and choline (Cho) at 3.22 ppm were calculated with FuncTool software (GE Healthcare, Milwaukee, WI, USA). Peak integral values were expressed relative to the Cr peak. Metabolite intensity ratios, including NAA/Cr ratios and Cho/Cr ratios, were calculated automatically at the end of each single-voxel acquisition. The NAA/Cho ratio was also calculated for comparison. To ensure high-quality images, MRS results with a full width at half maxima >6 Hz were disqualified from MRS analysis.


Association between proton magnetic resonance spectroscopy measurements and CAG repeat number in patients with spinocerebellar ataxias 2, 3, or 6.

Wang PS, Chen HC, Wu HM, Lirng JF, Wu YT, Soong BW - PLoS ONE (2012)

Representative cerebellar proton magnetic resonance (MR) spectra.(A) (Upper left) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper right) plane of the vermis in a normal subject at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (creatine [Cr]), red arrow (N-acetyl aspartate [NAA]), blue arrow (choline [Cho]), and yellow arrow (myoinositol [MI]). (B) (upper left) plane of the left hemisphere in a patient with spinocerebellar ataxia (SCA) at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a patient with SCA at which the MRS signal was acquired; (upper right) plane of the vermis in a patient with SCA at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (Cr), red arrow (NAA), blue arrow (Cho), and yellow arrow (MI).
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Related In: Results  -  Collection

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pone-0047479-g001: Representative cerebellar proton magnetic resonance (MR) spectra.(A) (Upper left) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a normal subject at which the MRS signal was acquired; (upper right) plane of the vermis in a normal subject at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (creatine [Cr]), red arrow (N-acetyl aspartate [NAA]), blue arrow (choline [Cho]), and yellow arrow (myoinositol [MI]). (B) (upper left) plane of the left hemisphere in a patient with spinocerebellar ataxia (SCA) at which the MRS signal was acquired; (upper middle) plane of the left hemisphere in a patient with SCA at which the MRS signal was acquired; (upper right) plane of the vermis in a patient with SCA at which the MRS signal was acquired; (lower panels) corresponding MR spectra with green arrow (Cr), red arrow (NAA), blue arrow (Cho), and yellow arrow (MI).
Mentions: Brain MRI and MRS were performed with a 1.5-T system (Signa EXCITE, GE Medical Systems, Milwaukee, WI, USA). The MRI protocol consisted of an axial, T1-weighted, three-dimensional, fast-spoiled, gradient-recalled acquisition of steady-state images (TR 8.58 msec, TE 3.62 msec, inversion time [TI] 400 msec, slice thickness 1.5 mm) and an axial, T2-weighted, fast spin-echo sequence (TR 4000 msec, TE 256.5 msec, slice thickness 5 mm). After MRI, proton MRS of the bilateral cerebellar hemispheres and the cerebellar vermis was performed with a single-voxel, stimulated echo-acquisition mode sequence (Fig. 1, TR/TE/mixing time/excitations: 3000/15/13.7/96; spectral width  = 2500 Hz, number of points  = 2048, voxel size  = 1.8±2 cm×2 cm ×2 cm). The voxel of interest (VOI) for each subject was selected so as to correspond to the anatomy of the region being investigated (cerebellar hemispheres and vermis) and was performed by the same investigator (JFL) to ensure consistent placement. Individual VOIs were confirmed by two additional investigators (HCC, HMW) from three-dimensional maps overlaid on T2-weighted images for further processing. Measurements were derived by the software associated with the MRI equipment. Care was taken to avoid cerebrospinal fluid–filled spaces within the VOIs. Peak areas for NAA at 2.02 parts per million (ppm), creatine (Cr) at 3.03 ppm, and choline (Cho) at 3.22 ppm were calculated with FuncTool software (GE Healthcare, Milwaukee, WI, USA). Peak integral values were expressed relative to the Cr peak. Metabolite intensity ratios, including NAA/Cr ratios and Cho/Cr ratios, were calculated automatically at the end of each single-voxel acquisition. The NAA/Cho ratio was also calculated for comparison. To ensure high-quality images, MRS results with a full width at half maxima >6 Hz were disqualified from MRS analysis.

Bottom Line: Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects.The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression.These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

View Article: PubMed Central - PubMed

Affiliation: Institute of Brain Science, National Yang-Ming University, Taipei, Taiwan.

ABSTRACT
The aim of this study was to correlate magnetic resonance spectroscopy (MRS) measurements, including that for the N-acetyl aspartate (NAA)/creatine (Cr) ratio in the vermis (denoted V-NAA), right cerebellar hemisphere (R-NAA), and left (L-NAA) cerebellar hemisphere, with the clinical scale for the assessment and rating of ataxia (SARA) score for patients with spinocerebellar ataxia (SCA) types 2, 3, and 6. A total of 24 patients with SCA2, 48 with SCA3, and 16 with SCA6 were recruited; 12 patients with SCA2, 43 with SCA3, and 8 with SCA6 underwent detailed magnetic resonance neuroimaging. Forty-four healthy, age-matched individuals without history of neurologic disease served as control subjects. V-NAA and patient age were used to calculate the predicted age at which a patient with SCA2 or SCA3 would reach an onset V-NAA value. Results showed the following: the NAA/Cr ratio decreased with increasing age in patients with SCA but not in control subjects; the SARA score increased progressively with age and duration of illness; V-NAA showed a better correlation with SARA score than R-NAA in patients with SCA2 or SCA3; the ratio of age to V-NAA correlated well with CAG repeat number; the retrospectively predicted age of onset for SCA2 and SCA3 was consistent with patient-reported age of onset; R-NAA showed a better correlation with SARA score than V-NAA in patients with SCA6; V-NAA and R-NAA correlated with clinical severity (SARA score) in patients with SCA. The correlation between CAG repeat number and age could be expressed as a simple linear function, which might explain previous observations claiming that the greater the CAG repeat number, the earlier the onset of illness and the faster the disease progression. These findings support the use of MRS values to predict age of disease onset and to retrospectively evaluate the actual age of disease onset in SCA.

Show MeSH
Related in: MedlinePlus