Clinical and neuroimaging characteristics of primary lateral sclerosis with overlapping features of progressive supranuclear palsy

Negin Badihian; Rodolfo G Gatto; Ryota Satoh; Farwa Ali; Heather M Clark; Nha Trang Thu Pham; Jennifer L Whitwell; Keith A Josephs

doi:10.1111/ene.16320

Clinical and neuroimaging characteristics of primary lateral sclerosis with overlapping features of progressive supranuclear palsy

Eur J Neurol. 2024 Apr 30:e16320. doi: 10.1111/ene.16320. Online ahead of print.

Authors

Negin Badihian¹, Rodolfo G Gatto¹, Ryota Satoh¹, Farwa Ali¹, Heather M Clark¹, Nha Trang Thu Pham², Jennifer L Whitwell², Keith A Josephs¹

Affiliations

¹ Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Radiology, Mayo Clinic, Rochester, Minnesota, USA.

PMID: 38686979
DOI: 10.1111/ene.16320

Abstract

Background and purpose: Primary lateral sclerosis (PLS) is a neurodegenerative disorder that primarily affects the central motor system. In rare cases, clinical features of PLS may overlap with those of progressive supranuclear palsy (PSP). We investigate neuroimaging features that can help distinguish PLS with overlapping features of PSP (PLS-PSP) from PSP.

Methods: Six patients with PLS-PSP were enrolled between 2019 and 2023. We compared their clinical and neuroimaging characteristics with 18 PSP-Richardson syndrome (PSP-RS) patients and 20 healthy controls. Magnetic resonance imaging, ¹⁸F-flortaucipir positron emission tomography (PET), quantitative susceptibility mapping, and diffusion tensor imaging tractography (DTI) were performed to evaluate eight brain regions of interest. Area under the receiver operating characteristic curve (AUROC) was calculated.

Results: Five of the six PLS-PSP patients (83.3%) were male. Median age at symptom onset was 61.5 (52.5-63) years, and all had mixed features of PLS and PSP. Volumes of the pallidum, caudate, midbrain, and cerebellar dentate were smaller in PSP-RS than PLS-PSP, providing good discrimination (AUROC = 0.75 for all). The susceptibilities in pallidum, midbrain, and cerebellar dentate were greater in PSP-RS compared to PLS-PSP, providing excellent discrimination (AUROC ≥ 0.90 for all). On DTI, fractional anisotropy (FA) in the posterior limb of the internal capsule from the corticospinal tract was lower in PLS-PSP compared to PSP-RS (AUROC = 0.86), but FA in the superior cerebellar peduncle was lower in PSP-RS (AUROC = 0.95). Pallidum flortaucipir PET uptake was greater in PSP-RS compared to PLS-PSP (AUROC = 0.74).

Conclusions: Regional brain volume, tractography, and magnetic susceptibility, but not tau-PET, are useful in distinguishing PLS-PSP from PSP.

Keywords: neurodegenerative disorders; primary lateral sclerosis; progressive supranuclear palsy; quantitative susceptibility mapping; tractography.

Abstract

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