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Contra-Directional Expression of Serum Homocysteine and Uric Acid as Important Biomarkers of Multiple System Atrophy Severity: A Cross-Sectional Study.

Chen D, Wei X, Zou J, Wang R, Liu X, Xu X, Lu J, Wang Z, Tang B, Wang B, Jin K, Wang Q - Front Cell Neurosci (2015)

Bottom Line: Serum Hcy was higher in MSA patients when compared to healthy subjects, particularly in male patients.Serum UA was lower in MSA patients when compared healthy subjects, particularly in male patients.Serum Hcy levels were significantly positively correlated with the severity of MSA.The ROC curve for the combination of Hcy and UA showed potential diagnostic value in discriminating MSA from healthy subjects.Compared with healthy subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were unchanged in MSA patients.Interestingly, there was a significant correlation between Hcy levels and MSA severity such as movement dysfunction, declined cognition, and cardiovascular symptoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.

ABSTRACT

Highlights: Serum Hcy was higher in MSA patients when compared to healthy subjects, particularly in male patients.Serum UA was lower in MSA patients when compared healthy subjects, particularly in male patients.Serum Hcy levels were significantly positively correlated with the severity of MSA.The ROC curve for the combination of Hcy and UA showed potential diagnostic value in discriminating MSA from healthy subjects.

Aim: There is evidence suggesting that inflammatory responses play a critical role in the pathogenesis of multiple system atrophy (MSA). Whether inflammatory mediators can be used as reliable biomarkers to detect the severity and progression of MSA remains largely unknown.

Methods: We performed a cross-sectional study that included 47 patients with MSA and 50 healthy age-matched controls. Serum levels of homocysteine (Hcy), uric acid (UA), and C-reactive protein (CRP) were measured. These levels positively correlated with the severity of MSA, based on both motor and non-motor symptoms. Several scales were used to rate the severity of MSA, including the Unified multiple system atrophy rating scale, Parkinson's disease sleep scale, Non-motor Symptoms Scale, the Schwab & England activities of daily living scale, Webster Scale, modified Hoehn and Yahr staging scale, and the Mini-Mental State Examination. Receiver operating characteristic (ROC) curves was applied to map the diagnostic accuracy of MSA against healthy subjects.

Results: Compared with healthy subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were unchanged in MSA patients. These findings were especially prominent in male patients. No significant differences of serum Hcy and UA were observed between patients of MSA and PD. Interestingly, there was a significant correlation between Hcy levels and MSA severity such as movement dysfunction, declined cognition, and cardiovascular symptoms. Additionally, the ROC curve for the combination of Hcy and UA (AUC 0.736) showed potential diagnostic value in discriminating MSA from healthy subjects.

Conclusion: Our findings suggest that the inflammatory mediators Hcy and UA may play important roles in the pathogenesis of MSA. The measurement of serum Hcy and UA levels could then be a useful tool to accurately distinguish MSA from healthy subjects.

No MeSH data available.


Related in: MedlinePlus

Representative MRI images of a patient with MSA. (A) Horizontal and (B) vertical hyperintensities in the pontine also known as “cross sign,” are shown in T2-weighted images. (C) Angle sign in the brainstem shown in a T2-weighted image. Red arrows indicate abnormalities pertaining to MSA.
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Figure 1: Representative MRI images of a patient with MSA. (A) Horizontal and (B) vertical hyperintensities in the pontine also known as “cross sign,” are shown in T2-weighted images. (C) Angle sign in the brainstem shown in a T2-weighted image. Red arrows indicate abnormalities pertaining to MSA.

Mentions: Experienced neurologists were recruited to perform the evaluations and complete the neurological examinations for both the inpatients and the outpatients. All patients with MSA included in this study satisfied the criteria outlined in Wenning’s study (Wenning and Krismer, 2013); the patients with PD fulfilled the criteria of the UK-PDSBB (Hughes et al., 1992). The exclusion criteria were as follows: (1) all patients with disability due to neurological disorders other than MSA/PD, such as cerebral vascular disease, the related sequelae, or psychosis; (2) participants with diseases that could possibly influence NMS including pain syndromes, advanced diabetes, mellitus, malignancy, renal, hepatic failure or cardiovascular diseases, severe anemia, or any other acute or chronic debilitating or life-threatening disease/state; and (3) individuals who refused to participate in the study. All subjects completed the following battery of standardized assessment measures: the UMSARS was used to evaluate motor dysfunction and disease severity; the scales included a historical review of disease-related impairments (I, 12 items; the range is 0–48 points; a higher score represents more severe disability), detailed motor examination (II, 14 items; 0–56 points), and a global disability scale (IV) (Geser et al., 2005). The H&Y and the ADL scales divided patients into stages on the basis of clinical disability (Kaufman et al., 2013). The Webster scale (10 items, total score ranging from 0 to 30 points) was applied to assess the degree of motor disability. The degree of NMS in every patient was measured by the NMSS and PDSS (Zhang et al., 2011; Pan et al., 2013). Cognitive abilities were evaluated with the MMSE (Barone et al., 2009; Pfeiffer, 2009). The typical magnetic resonance imaging (MRI) for MSA patients is shown in Figure 1. All scales were available and validated for the Chinese population. The demographics and clinical data of the subjects are shown in Table 2.


Contra-Directional Expression of Serum Homocysteine and Uric Acid as Important Biomarkers of Multiple System Atrophy Severity: A Cross-Sectional Study.

Chen D, Wei X, Zou J, Wang R, Liu X, Xu X, Lu J, Wang Z, Tang B, Wang B, Jin K, Wang Q - Front Cell Neurosci (2015)

Representative MRI images of a patient with MSA. (A) Horizontal and (B) vertical hyperintensities in the pontine also known as “cross sign,” are shown in T2-weighted images. (C) Angle sign in the brainstem shown in a T2-weighted image. Red arrows indicate abnormalities pertaining to MSA.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492156&req=5

Figure 1: Representative MRI images of a patient with MSA. (A) Horizontal and (B) vertical hyperintensities in the pontine also known as “cross sign,” are shown in T2-weighted images. (C) Angle sign in the brainstem shown in a T2-weighted image. Red arrows indicate abnormalities pertaining to MSA.
Mentions: Experienced neurologists were recruited to perform the evaluations and complete the neurological examinations for both the inpatients and the outpatients. All patients with MSA included in this study satisfied the criteria outlined in Wenning’s study (Wenning and Krismer, 2013); the patients with PD fulfilled the criteria of the UK-PDSBB (Hughes et al., 1992). The exclusion criteria were as follows: (1) all patients with disability due to neurological disorders other than MSA/PD, such as cerebral vascular disease, the related sequelae, or psychosis; (2) participants with diseases that could possibly influence NMS including pain syndromes, advanced diabetes, mellitus, malignancy, renal, hepatic failure or cardiovascular diseases, severe anemia, or any other acute or chronic debilitating or life-threatening disease/state; and (3) individuals who refused to participate in the study. All subjects completed the following battery of standardized assessment measures: the UMSARS was used to evaluate motor dysfunction and disease severity; the scales included a historical review of disease-related impairments (I, 12 items; the range is 0–48 points; a higher score represents more severe disability), detailed motor examination (II, 14 items; 0–56 points), and a global disability scale (IV) (Geser et al., 2005). The H&Y and the ADL scales divided patients into stages on the basis of clinical disability (Kaufman et al., 2013). The Webster scale (10 items, total score ranging from 0 to 30 points) was applied to assess the degree of motor disability. The degree of NMS in every patient was measured by the NMSS and PDSS (Zhang et al., 2011; Pan et al., 2013). Cognitive abilities were evaluated with the MMSE (Barone et al., 2009; Pfeiffer, 2009). The typical magnetic resonance imaging (MRI) for MSA patients is shown in Figure 1. All scales were available and validated for the Chinese population. The demographics and clinical data of the subjects are shown in Table 2.

Bottom Line: Serum Hcy was higher in MSA patients when compared to healthy subjects, particularly in male patients.Serum UA was lower in MSA patients when compared healthy subjects, particularly in male patients.Serum Hcy levels were significantly positively correlated with the severity of MSA.The ROC curve for the combination of Hcy and UA showed potential diagnostic value in discriminating MSA from healthy subjects.Compared with healthy subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were unchanged in MSA patients.Interestingly, there was a significant correlation between Hcy levels and MSA severity such as movement dysfunction, declined cognition, and cardiovascular symptoms.

View Article: PubMed Central - PubMed

Affiliation: Department of Neurology, The Third Affiliated Hospital of Sun Yat-Sen University , Guangzhou , China.

ABSTRACT

Highlights: Serum Hcy was higher in MSA patients when compared to healthy subjects, particularly in male patients.Serum UA was lower in MSA patients when compared healthy subjects, particularly in male patients.Serum Hcy levels were significantly positively correlated with the severity of MSA.The ROC curve for the combination of Hcy and UA showed potential diagnostic value in discriminating MSA from healthy subjects.

Aim: There is evidence suggesting that inflammatory responses play a critical role in the pathogenesis of multiple system atrophy (MSA). Whether inflammatory mediators can be used as reliable biomarkers to detect the severity and progression of MSA remains largely unknown.

Methods: We performed a cross-sectional study that included 47 patients with MSA and 50 healthy age-matched controls. Serum levels of homocysteine (Hcy), uric acid (UA), and C-reactive protein (CRP) were measured. These levels positively correlated with the severity of MSA, based on both motor and non-motor symptoms. Several scales were used to rate the severity of MSA, including the Unified multiple system atrophy rating scale, Parkinson's disease sleep scale, Non-motor Symptoms Scale, the Schwab & England activities of daily living scale, Webster Scale, modified Hoehn and Yahr staging scale, and the Mini-Mental State Examination. Receiver operating characteristic (ROC) curves was applied to map the diagnostic accuracy of MSA against healthy subjects.

Results: Compared with healthy subjects, we found that serum Hcy was higher, UA was lower, and CRP levels were unchanged in MSA patients. These findings were especially prominent in male patients. No significant differences of serum Hcy and UA were observed between patients of MSA and PD. Interestingly, there was a significant correlation between Hcy levels and MSA severity such as movement dysfunction, declined cognition, and cardiovascular symptoms. Additionally, the ROC curve for the combination of Hcy and UA (AUC 0.736) showed potential diagnostic value in discriminating MSA from healthy subjects.

Conclusion: Our findings suggest that the inflammatory mediators Hcy and UA may play important roles in the pathogenesis of MSA. The measurement of serum Hcy and UA levels could then be a useful tool to accurately distinguish MSA from healthy subjects.

No MeSH data available.


Related in: MedlinePlus