Altered cerebral blood flow in patients with spinocerebellar degeneration

Abstract

Objectives: Spinocerebellar degeneration (SCD) comprises a multitude of disorders with sporadic and hereditary forms, including spinocerebellar ataxia (SCA). Except for progressive cerebellar ataxia and structural atrophy, hemodynamic changes have also been observed in SCD. This study aimed to explore the whole-brain patterns of altered cerebral blood flow (CBF) and its correlations with disease severity and psychological abnormalities in SCD via arterial spin labeling (ASL).

Methods: Thirty SCD patients and 30 age- and sex-matched healthy controls (HC) were prospectively recruited and underwent ASL examination on a 3.0T MR scanner. The Scale for Assessment and Rating of Ataxia (SARA) and the International Cooperative Ataxia Rating Scale (ICARS) scores were used to evaluate the disease severity in SCD patients. Additionally, the status of anxiety, depression and sleep among all patients were, respectively, evaluated by the Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) and Self-Rating Scale of Sleep (SRSS). We compared the whole-brain CBF value between SCD group and HC group at the voxel level. Then, the correlation analyses between CBF and disease severity, and psychological abnormalities were performed on SCD group.

Results: Compared with HC, SCD patients demonstrated decreased CBF value in two clusters (FWE corrected P < 0.05), covering bilateral dentate and fastigial nuclei, bilateral cerebellar lobules I-IV, V and IX, left lobule VI, right lobule VIIIb, lobules IX and X of the vermis in the cerebellar Cluster 1 and the dorsal part of raphe nucleus in the midbrain Cluster 2. The CBF of cerebellar Cluster 1 was negatively correlated with SARA scores (Spearman's rho = -0.374, P = 0.042) and SDS standard scores (Spearman's rho = -0.388, P = 0.034), respectively. And, the CBF of midbrain Cluster 2 also had negative correlations with SARA scores (Spearman's rho = -0.370, P = 0.044) and ICARS scores (Pearson r = -0.464, P = 0.010).

Conclusion: The SCD-related whole-brain CBF changes mainly involved in the cerebellum and the midbrain of brainstem, which are partially overlapped with the related function cerebellar areas of hand, foot and tongue movement. Decreased CBF was related to disease severity and depression status in SCD. Therefore, CBF may be a promising neuroimaging biomarker to reflect the severity of SCD and suggest mental changes.

Keywords: arterial spin labeling; cerebellum; cerebral blood flow; spinocerebellar ataxia; spinocerebellar degeneration.

FIGURE 1

Detailed visualization for voxel-based HC > SCD comparison across groups using normalized CBF values performed by the two-sample t-test with a threshold of P < 0.05 (FWE corrected) and cluster size of 10 voxels. The warm color represents voxels with significantly decreased CBF in the SCD group compared with the HC group. Results of the HC < SCD comparison are not shown because no significant voxel was detected under the same FWE correction threshold and cluster size. (A) Cluster 1 shown in yellow/red, overlaid onto the cerebellar atlas (Diedrichsen et al., 2009) in coronal slices. Cerebellar lobules and nucleus are marked in red on the right cerebellum. (B) Top row: magnified Cluster 2 shown in yellow/red; Bottom row: Cluster 2 with AAL3 brain region mapped on. HC, healthy control; SCD, spinocerebellar degeneration; CBF, cerebral blood flow; FWE, family-wise error; Roman numerals I-X, number of cerebellar hemisphere lobules (Schmahmann et al., 1999); D, dentate nucleus; F, fastigial nucleus; Raphe_D, dorsal raphe nucleus (Rolls et al., 2020); L, left; R, right; x,y,z, space coordinates.

FIGURE 2

Visualization on flatmaps for cerebellar-located Cluster 1. (A) The t-map of Normalized CBF group results (HC > SCD) projected to the cerebellar SUIT flatmap. Regions displayed in warm colors represent the significant CBF decrease in SCD patients. (B) Outline curves of results in flatmap (A) shown in white dotted lines are overlaid onto the flatmap of anatomical distributions for cerebellar lobules I-X. Note that for lobule VI-X, two hemispheric and one vermal compartment (displayed in slightly different colors) are defined. (C) Outline curves of results in flatmap (A) shown in white dotted lines are overlaid onto the flatmap of the sensorimotor topography for activation related to hand, foot and tongue movement activations. HC, healthy control; SCD, spinocerebellar degeneration; L, left; R, right; V, vermis; H, hemisphere; Roman numerals I-X, number of cerebellar lobules (Schmahmann et al., 1999).

FIGURE 3

There were statistically significant differences in normalized CBF of ROI-based Cluster 1 and Cluster 2 between the SCD group and the HC group. SCD, spinocerebellar degeneration. ^** indicates P < 0.0001.

FIGURE 4

Correlations between the normalized CBF values and clinical characteristics. The normalized CBF of Cluster 1 had a negative correlation with SARA scores (A) and SDS standard scores (B), respectively. For Cluster 2, the normalized CBF was also negatively correlated with SARA scores (C) and ICARS scores (D), respectively. CBF, cerebral blood flow; SARA, scale for assessment and rating of ataxia; SDS, self-rating depression scale; ICARS, international cooperative ataxia rating scale.