Objective: To validate the accuracy of the newly proposed Movement Disorder Society diagnostic criteria for progressive supranuclear palsy (MDS-PSP criteria, Höglinger et al., 2017) to predict an underlying 4R-tauopathy.

Background: PSP and corticobasal degeneration (CBD) are tauopathies with predominant aggregation of 4-repeat tau. Clinically, they are often difficult to differentiate, since the symptoms of PSP and CBD overlap. Since PSP and CBD share many pathological mechanisms, joint clinical recognition as 4R-tauopathies may offer unique opportunities for neurobiological investigations and therapeutic interventions. Therefore, the MDS-PSP criteria introduced a new category for “probable 4R-tauopathies”, comprising patients with a diagnosis of “probable PSP” (any phenotype), “possible PSP with speech/language dysfunction (PSP-SL)” and “possible PSP with corticobasal syndrome (CBS)”. The diagnostic accuracy of this category has not yet been validated.

Method: Autopsy-confirmed patients with a pathological diagnosis of PSP and CBD (jointly grouped as 4R-tauopathies), and PD, MSA and FTLD (jointly grouped as non-4R-tauopathies) were identified. Detailed clinical information was obtained for each case by retrospective chart review. Accuracy of the MDS-PSP criteria for 4R-tauopathies was analyzed after retrospective application to this case series.

Results: We identified 250 cases with a 4R-tauopathy (PSP: 195, CBD: 55) and 161 cases with a non-4R-tauopathy (PD: 51, MSA: 50, FTLD: 60) with detailed clinical information from multiple brain banks. In the first 2 years of disease, a diagnosis of “probable 4R-tauopathy” as defined in the MDS-PSP criteria had a sensitivity of 19% and a specificity of 99% for 4R-tauopathies. At final record, a diagnosis of “probable 4R-tauopathy” had a sensitivity of 59% and a specificity of 88%. Sensitivity for CBD was lower (38%) than for PSP (65%).

Conclusion: The new diagnostic category for “probable 4R-tauopathies”, defined by the MDS-PSP criteria, shows high specificity for 4R-tauopathies and may be suitable for joint recruitment of patients into therapeutic trials targeting 4R-tau.

References: Höglinger et al. Clinical diagnosis of progressive supranuclear palsy: The movement disorder society criteria. Mov Disord. 2017;32:853-864.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/validation-of-the-movement-disorder-society-criteria-for-the-diagnosis-of-4r-tauopathies/