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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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Changes in N-acetyl aspartate/creatine ratio (NAA) with age and CAG repeat number.Changes in NAA ratio with age were related to the number of CAG repeats in patients with spinocerebellar ataxia 2 (SCA2) (A) or SCA3 (C). In A and C, the onset vermis NAA value (V-NAA) was calculated based on the correlation of the scale for the assessment and rating of ataxia (SARA) score and V-NAA and was used to retrospectively predict the age of onset of for CAG repeat group. The predicted age of onset and the average reported age of onset are plotted in B (SCA2) and D (SCA3). The error bars denote the standard deviation of reported ages.
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pone-0047479-g002: Changes in N-acetyl aspartate/creatine ratio (NAA) with age and CAG repeat number.Changes in NAA ratio with age were related to the number of CAG repeats in patients with spinocerebellar ataxia 2 (SCA2) (A) or SCA3 (C). In A and C, the onset vermis NAA value (V-NAA) was calculated based on the correlation of the scale for the assessment and rating of ataxia (SARA) score and V-NAA and was used to retrospectively predict the age of onset of for CAG repeat group. The predicted age of onset and the average reported age of onset are plotted in B (SCA2) and D (SCA3). The error bars denote the standard deviation of reported ages.

Mentions: We also found that patients with SCA exhibited differences in CAG repeat number. When they were grouped based on CAG repeat number, the decrease of NAA ratio with age was more obvious (Fig. 2A, C). Overall, the greater the CAG repeat number, the earlier the decrease occurred, especially in patients with SCA2. Notably, in patients with SCA3, the greater the CAG repeat number, the faster the disease progression. When two or more NAA ratios (at different time points) were available, the change in NAA ratio could be used to predict the rate of disease progression. To test this, data from patients with similar CAG repeat numbers were used to predict age of disease onset. The V-NAA and AS of these patients were used to calculate the age at which the patient had a predicted onset V-NAA. As mentioned above, at the onset of SCA2 or SCA3, the V-NAA values were 0.7866 and 0.8576, respectively. The calculated age was considered the retrospectively predicted AO of the patient with the corresponding CAG repeat number. Interestingly, the average reported AO showed a good correlation with the predicted AO (Fig. 2B, SCA2, r = 0.996, P<0.001; Fig. 2D, SCA3, r = 0.866, P<0.001).


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)

Changes in N-acetyl aspartate/creatine ratio (NAA) with age and CAG repeat number.Changes in NAA ratio with age were related to the number of CAG repeats in patients with spinocerebellar ataxia 2 (SCA2) (A) or SCA3 (C). In A and C, the onset vermis NAA value (V-NAA) was calculated based on the correlation of the scale for the assessment and rating of ataxia (SARA) score and V-NAA and was used to retrospectively predict the age of onset of for CAG repeat group. The predicted age of onset and the average reported age of onset are plotted in B (SCA2) and D (SCA3). The error bars denote the standard deviation of reported ages.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3475643&req=5

pone-0047479-g002: Changes in N-acetyl aspartate/creatine ratio (NAA) with age and CAG repeat number.Changes in NAA ratio with age were related to the number of CAG repeats in patients with spinocerebellar ataxia 2 (SCA2) (A) or SCA3 (C). In A and C, the onset vermis NAA value (V-NAA) was calculated based on the correlation of the scale for the assessment and rating of ataxia (SARA) score and V-NAA and was used to retrospectively predict the age of onset of for CAG repeat group. The predicted age of onset and the average reported age of onset are plotted in B (SCA2) and D (SCA3). The error bars denote the standard deviation of reported ages.
Mentions: We also found that patients with SCA exhibited differences in CAG repeat number. When they were grouped based on CAG repeat number, the decrease of NAA ratio with age was more obvious (Fig. 2A, C). Overall, the greater the CAG repeat number, the earlier the decrease occurred, especially in patients with SCA2. Notably, in patients with SCA3, the greater the CAG repeat number, the faster the disease progression. When two or more NAA ratios (at different time points) were available, the change in NAA ratio could be used to predict the rate of disease progression. To test this, data from patients with similar CAG repeat numbers were used to predict age of disease onset. The V-NAA and AS of these patients were used to calculate the age at which the patient had a predicted onset V-NAA. As mentioned above, at the onset of SCA2 or SCA3, the V-NAA values were 0.7866 and 0.8576, respectively. The calculated age was considered the retrospectively predicted AO of the patient with the corresponding CAG repeat number. Interestingly, the average reported AO showed a good correlation with the predicted AO (Fig. 2B, SCA2, r = 0.996, P<0.001; Fig. 2D, SCA3, r = 0.866, P<0.001).

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