The Inferior Cerebellar Peduncle Sign: A Novel Imaging Marker for Differentiating Multiple System Atrophy Cerebellar Type from Spinocerebellar Ataxia

BACKGROUND AND PURPOSE: The hot cross bun (HCB) sign is a hallmark feature of multiple system atrophy with predominant cerebellar ataxia (MSA-C), typically observed in advanced stages of the disease; however, it can also present in other conditions such as spinocerebellar ataxia (SCA), making the differentiation challenging. The middle cerebellar peduncle (MCP) sign may be observed in various medical conditions and in healthy individuals. We hypothesized that the inferior cerebellar peduncle (ICP), known to be affected in MSA-C, may exhibit hyperintensity on fluid-attenuated inversion recovery (FLAIR) imaging, potentially aiding in differentiating MSA-C from SCA.

MATERIALS AND METHODS: Medical records of 153 probable MSA-C and 72 genetically confirmed SCAs from a single institution were reviewed retrospectively between January 2012 and June 2023. MRI was performed using 3-Tesla scanners. The ICP sign was deemed positive when the bilateral ICP signal intensity exceeded that of the medulla oblongata on axial FLAIR images. MCP and HCB signs were also evaluated. Two independent neuroradiologists evaluated all MRIs, and interobserver agreement was assessed using Kappa statistics. Univariable and multivariable logistic regression analyses identified predictive features and diagnostic performance was assessed.

RESULTS: The ICP sign was more prevalent in patients with MSA-C (65%) compared to those with SCA (6.9%; P < .001). HCB and MCP signs were more frequent in patients with MSA-C (n = 110 and n = 134) than in those with SCA (n = 19 and n = 30; P<.001). The ICP sign demonstrated the highest specificity (95%) for predicting MSA-C, with an AUC of 0.82, respectively. The MCP sign exhibited superior sensitivity (87%) but lower specificity and AUC compared to the ICP sign. Combining the ICP and MCP signs improved the AUC to 0.86. Integrating clinical features (age, sex, and disease duration) with imaging features yielded excellent diagnostic performance, with an AUC of 0.98.

CONCLUSIONS: The ICP sign on FLAIR imaging exhibits high specificity in distinguishing MSA-C from SCA. Integrating clinical and imaging features further enhances diagnostic accuracy, potentially improving differential diagnosis in clinical settings of cerebellar ataxia.

ABBREVIATIONS: AUC = area under the curve; HCB = hot cross bun; ICP = inferior cerebellar peduncle; ICI = integrated calibration index; IQR = interquartile range; IRB = Institutional Review Board; MCP = middle cerebellar peduncle; MDS = Movement Disorder Society; MSA = multiple system atrophy; MSA-C = multiple system atrophy with predominant cerebellar ataxia; SCA = spinocerebellar ataxia.