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

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.

FIGURE 1

Partial tractography reconstructions from diffusion tensor imaging techniques. The corticospinal tracts (CSTs) in yellow were partially reconstructed and centered in a region representing the right (red) and left (blue) posterior limb of the internal capsule (PLIC). The superior cerebellar peduncle (SCP) was also reconstructed (green). The lateral ventricular system (LV) is represented as a topographical reference (purple). CST_l, left CST; CST_r, right CST; R, right.

FIGURE 2

Fluorodeoxyglucose positron emission tomography scan of patients with primary lateral sclerosis with overlapping features of progressive supranuclear palsy. L, left; R, right; Sup, superior.

FIGURE 3

Quantitative susceptibility mapping images of representative progressive supranuclear palsy (PSP)–Richardson syndrome (PSP‐RS) and primary lateral sclerosis (PLS)‐PSP patients. The PSP‐RS patient has greater susceptibility signals than the PLS‐PSP patient in the pallidum, substantia nigra, red nucleus, and cerebellar dentate.