Peripheral Inflammation Profile of Cerebellar Ataxia

Abstract

Objectives: The objective of this study is to determine the characteristics of peripheral inflammatory profiles and their correlations with the clinical features in patients with cerebellar ataxia.

Methods: We conducted a cross-sectional study on a cohort of 140 cerebellar ataxia patients, including 74 patients with spinocerebellar ataxia (SCA), 66 patients with multiple system atrophy with predominant cerebellar ataxia (MSA-C), and 145 healthy controls (HCs). Inflammatory profiles (PLT, MPV, NLR, PLR, MLR, SII, AISI and ESR) were measured in peripheral blood, and were compared by ANOVA and Kruskal-Wallis test. The receiver operating characteristic (ROC) curve and the area under curve (AUC) were performed to determine the sensitivity and specificity of the inflammatory markers. Spearman correlation and partial correlation analysis were performed to detect the association between inflammatory profiles and clinical scales in cerebellar ataxia.

Results: Inflammatory profiles from peripheral blood showed significant difference between different groups. Significant variations were observed in MPV, NLR, MLR, SII, AISI and ESR between cerebellar ataxia and HCs groups (p<0.05). NLR and ESR in both SCA and MSA-C groups were increased compared with HCs (p<0.05). The difference of MHR between SCA and MSA-C groups was observed based on HDL variation (p<0.05). The combination of ESR and PLT distinguished SCA from MSA-C (AUC=0.800). In addition, MLR was significantly corelated with clinical scales, including SARA and ICARS in SCA group as well as UMSARS and FAB in MSA-C group (r>0.3/r<-0.3).

Conclusion: Significant variation in peripheral inflammatory profiles was firstly identified in Chinese genetic ataxias and non-genetic cerebellar ataxia cohort, which showed the potential clinical correlations between peripheral inflammatory phenotype and severity of ataxia.

Keywords: Cerebellar ataxia; RNA.; biomarkers; blood routine examination; peripheral inflammation; receiver operating characteristic (ROC).

Fig. (1)

Altered peripheral inflammatory in HCs, SCAs and MSA-C subjects. The figures shows (A) NLR, (B) MLR, (C) AISI and (D) ESR levels in all three groupsparticipants: HCs, SCA and MSA-C. Variables were compared among three groups by one-way ANOVA for normally distributed data or the Kruskal-Wallis test for abnormally distributed data. P values of the posterior comparisons were adjusted by Bonferroni correction. Abbreviations: HCs, healthy controls, NLR, neutrophils-to-lymphocyte ratio, MLR, monocytes-to-lymphocyte ratio, AISI, aggregate Index of Systemic Inflammation, ESR, erythrocyte sedimentation rate, SCA, spinocerebellar ataxia, MSA-C, multiple system atrophy with predominant cerebellar ataxia. *p<0.05; **p<0.01; ***p<0.001 (Bonferroni corrected).

Fig. (2)

Correlation analysis between inflammatory markers and the severity of ataxia was presented. (A) MLR, (B) MHR and (C) NHR were positively correlated with SARA total score in SCA group. In MSA-C group, (D) NLR, (E) MHR and (F) were correlated with severity of disease. All SCAs patients carried out SARA, ICARS, BI and MMSE (n=52) and MSA-C patients carried out UMSARS, MMSE, SCOPA-AUT, Wexner, and FAB (n=28) were included. R values and p values calculated using Pearson correlation or Spearman correlation coefficient analysis are indicated on each dot plot. After Bonferroni correction, adjusted p values were non-significant. Abbreviations: MLR, monocytes-to-lymphocyte ratio, MHR, monocyte to high-density lipoprotein ratio. NHR, neutrophil to high-density lipoprotein ratio, NLR, neutrophils-to-lymphocyte ratio, ESR, erythrocyte sedimentation rate, SARA, the Scale for the Assessment and Rating of Ataxia. UMSARS, the Unified Multiple System Atrophy Rating Scale, FAB, Frontal Assessment Battery, SCA, spinocerebellar ataxia, MSA-C, multiple system atrophy with predominant cerebellar ataxia.

Fig. (3)

Comparisons of peripheral inflammation in different groups of SCAs and MSA-C patients. Higher levels of (A) MLR and (B) AISI were associated with moderateto-severe SCA groups, and (C) NHR showed an increasing trend. In MSA-C group, (D) NLR and (E) MLR showed no difference in these groups while (F) ESR increased in the severe groups. SCAs patients were divided into mild group (SARA <10, n=22) and moderate-to-severe group (SARA ≥10, n=30). MSA-C patients were divided into the mild group (UMSARS <29.5, n=14) and severe group (UMSARS>29.5, n=14). Variables were compared by independent sample t-test for normally distributed data or Mann-Whitney U test for abnormally distributed data. Abbreviations: MLR, monocytes-to-lymphocyte ratio, AISI, aggregate Index of Systemic Inflammation, NHR, neutrophil to high-density lipoprotein ratio, NLR, neutrophils-to-lymphocyte ratio, ESR, erythrocyte sedimentation rate, SCA, spinocerebellar ataxia, MSA-C, multiple system atrophy with predominant cerebellar ataxia.