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Frontal hypometabolism in the diagnosis of progressive supranuclear palsy clinical variants

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Abstract

Objective

Frontal hypometabolism on FDG-PET is observed in progressive supranuclear palsy (PSP), although it is unclear whether it is a feature of all PSP clinical variants and hence whether it is a useful diagnostic feature. We aimed to compare the frequency, severity, and pattern of frontal hypometabolism across PSP variants and determine whether frontal hypometabolism is related to clinical dysfunction.

Methods

Frontal hypometabolism in prefrontal, premotor, and sensorimotor cortices was visually graded on a 0–3 scale using CortexID Z-score images in 137 PSP patients. Frontal asymmetry was recorded. Severity scores were used to categorize patients as premotor-predominant, prefrontal-predominant, sensorimotor-predominant, mixed-predominance, or no regional predominance. Frontal ratings were compared across PSP clinical variants, and Spearman correlations were used to assess relationships with the Frontal Assessment Battery (FAB).

Results

97% showed evidence of frontal hypometabolism which was most common (100%) in the speech–language (PSP-SL), corticobasal (PSP-CBS), and frontal (PSP-F) variants and least common in the progressive gait freezing (PSP-PGF) variant (73%). PSP-SL and PSP-CBS showed more severe hypometabolism than Richardson’s syndrome (PSP-RS), Parkinsonism (PSP-P), and PSP-PGF. A premotor-predominant pattern was most common in PSP-SL and PSP-CBS, with more mixed patterns in the other variants. Hypometabolism was most commonly asymmetric in PSP-SL, PSP-P, PSP-F and PSP-CBS. Worse hypometabolism in nearly all frontal regions correlated with worse scores on the FAB.

Conclusions

Frontal hypometabolism is a common finding in PSP, although it varies in severity and pattern across PSP variants and will likely be the most diagnostically useful in PSP-SL and PSP-CBS.

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Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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Acknowledgements

The authors would like to acknowledge Dr. Dennis Dickson, Mayo Clinic, for performing the autopsy evaluations. This study was funded by the National Institutes of Health Grants R01-NS89757, R01-DC12519 and R01-DC14942.

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Authors and Affiliations

  1. Department of Neurology, Mayo Clinic, Rochester, MN, USA

    Jack A. Black, Farwa Ali & Keith A. Josephs

  2. Department of Radiology, Mayo Clinic, Rochester, MN, USA

    Nha Trang Thu Pham, Val J. Lowe & Jennifer L. Whitwell

  3. Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN, USA

    Mary M. Machulda

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Correspondence to Jennifer L. Whitwell.

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This study was approved by the Mayo Clinic IRB with informed consent obtained from all patients.

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Black, J.A., Pham, N.T.T., Ali, F. et al. Frontal hypometabolism in the diagnosis of progressive supranuclear palsy clinical variants. J Neurol (2024). https://doi.org/10.1007/s00415-024-12350-z

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