MRl and MRS hints for the differentiation of cerebellar multiple system atrophy from spinocerebellar ataxia type II

Abstract

Background and objectives: The differentiation of spinocerebellar ataxia type II (SCA 2) from idiopathic multiple systemic atrophy of the cerebellar type (MSA-C) is often difficult in patients with cerebellar ataxia when molecular testing is not available. Besides genetic testing, magnetic resonance imagining (MRI) and magnetic resonance spectroscopy (MRS) prove to be beneficial. Nevertheless, the characteristics observed through radiology change as the disease advances. Different radiological criteria may be needed across different stages of the disease. This study aimed to assess the radiological characteristics of MSA-C or SCA 2 patients across various stages of the disease and to identify potential distinguishing factors.

Methods: Between January 2000 and January 2020, a total of 390 patients, diagnosed with probable MSA-C according to the second consensus on MSA (317 cases) or with molecularly confirmed SCA 2 (73 cases), who had undergone at least one brain MRI and MRS targeting the cerebellar hemispheres, were enrolled in the study. The clinical parameters and neuroimaging features between these two diseases were compared and analyzed.

Results: A greater occurrence of a pontine hot cross bun sign (HCBS), higher scores on the scale for the assessment and rating of ataxia, and reduced levels of cerebellar N-acetyl aspartate (NAA)/creatine (Cr), and cerebellar choline (Cho)/Cr were found in MSA-C patients as compared with SCA 2 patients at similar disease durations. For the patients with an HCBS, a cerebellar Cho/Cr level of <0.53 was indicative of the potential presence of MSA-C, with significant level of specificity (85.96%).

Discussion: Discerning SCA2 from MSA-C using MRI and MRS appears to be plausible at various disease stages.

Keywords: HCBS; MRI; MRS; MSA-C; SCA2.

Fig. 1

The flowchart of patient inclusion details.

Fig. 2

Positioning of Magnetic Resonance Spectroscopy (MRS) Voxel of Interest (VOI). The VOIs for the cerebellar regions were precisely located at the center of the right (A) and left (B) cerebellar hemispheres, while the VOI for the vermis was centered within the vermis (C).

Fig. 3

The distribution plots of cerebellar NAA/Cr and cerebellar Cho/Cr with MSA or SCA2 across different disease durations. Specifically, panels A and B illustrate the distribution of NAA/Cr ratios, while panels C and D depict Cho/Cr ratios. For disease durations of 0–4 years (A and C) and durations exceeding 4 years (B and D), MSA-C patients exhibit significantly lower NAA/Cr and Cho/Cr ratios compared to those with SCA2.

Fig. 4

Distribution plots depicting the ratios of NAA/Cr in the cerebellum (A) and Cho/Cr in the cerebellum (B) for patients with HCBS-positive MSA-C or SCA2. It is observed that patients diagnosed with MSA-C exhibit significantly lower cerebellar Cho/Cr ratios when compared with those diagnosed with SCA2.

Fig. 5

Comparative distribution plots illustrating cerebellar NAA/Cr and Cho/Cr ratios in patients diagnosed with MSA-C or SCA2, stratified by various SARA scores. In individuals with SARA scores from 0 to 11, MSA-C patients exhibited significantly lower cerebellar NAA/Cr ratios compared to SCA2 patients (A), without significant changes in cerebellar Cho/Cr ratios (D). For those with SARA scores between 12 and 20, both cerebellar NAA/Cr (B) and Cho/Cr ratios (E) were significantly lower in MSA-C patients. In patients with severe disease, indicated by SARA scores of 21–40, MSA-C patients had lower cerebellar Cho/Cr ratios (F), but no significant difference in cerebellar NAA/Cr ratios (C) was observed.

Fig. 6

This figure showcases axial FLAIR images of the pons and cerebellar MRS data for patients diagnosed with MSA-C (A–F) and SCA2 (G–L), categorized by disease duration and segmented according to SARA scores into three ranges: 0–11 (A, B, G, H), 12–20 (C, D, I, J), and over 21 (E, F, K, L). Through showcasing patient profiles from the early to advanced stages of MSA-C and SCA2, highlight the utility of MRS readouts in differentiating between these conditions at various stages of disease progression, demonstrating the potential of specific metabolite ratios as diagnostic markers.