Objective: This review evaluates limitations in differentiating underlying pathologies in Corticobasal syndrome (CBS). We summarize available evidence on clinical features, imaging and fluid biomarkers and highlight emerging neuroimaging techniques that may improve diagnostic criteria.

Background: Corticobasal syndrome (CBS) and Corticobasal degeneration (CBD) are frequently conflated despite representing different entities. CBD is an atypical Parkinsonian disorder characterized by abnormal 4-repeat phosphorylated tau deposition in cortical and subcortical regions and is one of the most common underlying pathologies of CBS. Other pathologies include Frontotemporal lobar degeneration (FTLD), Alzheimer’s disease (AD) and Progressive supranuclear palsy (PSP). Although diagnostic neuroimaging and fluid biomarkers have improved, distinguishing the underlying pathology remains a challenge.

Method: We reviewed publications from 1999–2025, examining clinical, pathological, neuroimaging and biomarker features associated with CBS in order to assess current diagnostic approaches and their limitations in identifying underlying pathologies.

Results: Structural Magnetic Resonance Imaging (MRI) in CBS often exhibits asymmetric frontoparietal atrophy involving the Perirolandic cortex and Basal Ganglia, while FDG-PET frequently reveals asymmetric frontoparietal hypometabolism. These findings are nonspecific and seen in other pathologies like FTLD, PSP, and AD. Similarly, Tau-PET has limited sensitivity for 4-repeat tauopathies like CBD. Fluid biomarkers such as serum or cerebrospinal fluid phosphorylated tau and neurofilament light chains, have helped identify AD-related pathologies in CBS, though overall no current diagnostic measures have reliably characterized underlying pathologies in CBS. Recent advances in ultra-high-field MRI including 7-Tesla MRI, have demonstrated better sensitivity to detect disease-specific changes in neurodegenerative disorders showing prospective applications in CBS.

Conclusion: Differentiating underlying pathologies in CBS remains a major challenge. While current methods and biomarkers contribute valuable information, they lack specificity to reliably identify CBD. Integrating emerging fluid biomarkers with advanced neuroimaging modalities, including ultra-high-field 7-Tesla MRI, may improve the identification of disease-specific structural patterns and enhance diagnostic precision in CBS.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/emerging-roles-for-imaging-techniques-in-differentiating-underlying-pathologies-in-corticobasal-syndrome/