Tau-PET and multimodal imaging in clinically atypical multiple system atrophy masquerading as progressive supranuclear palsy. (August 2022)

• Record Type: Journal Article
• Authors: Carlos, Arenn F.; Sekiya, Hiroaki; Koga, Shunsuke; Pham, Nha Trang Thu; Ali, Farwa; Botha, Hugo; Clark, Heather M.; Coon, Elizabeth A.; Lowe, Val; Ahlskog, J. Eric; Trejo-Lopez, Jorge A.; Dickson, Dennis W.; Whitwell, Jennifer L.; Josephs, Keith A.
• Is Part Of: Parkinsonism & related disorders. Volume 101(2022)
• Page Start: 9
• Page End: 14
• Publication Date: 2022-08
• Subjects: Atypical MSA -- PSP phenotype -- MRI planimetry -- Flortaucipir-PET -- FDG-PET; Parkinson's disease -- Periodicals; Movement disorders -- Periodicals; Movement Disorders -- Periodicals; Nerve Degeneration -- Periodicals; Nervous System Diseases -- Periodicals; Parkinson Disease -- Periodicals; Tremor -- Periodicals; Parkinson, Maladie de -- Périodiques; Parkinson's disease; 616.833
• DOI: 10.1016/j.parkreldis.2022.06.008
• Languages: English
• ISSNs: 1353-8020

Abstract

Abstract: Introduction: Multiple system atrophy (MSA) typically presents with parkinsonism, ataxia and/or autonomic dysfunction. Occasionally, clinically atypical (ca-MSA) cases masquerade as progressive supranuclear palsy (PSP). We aimed to investigate whether different neuroimaging modalities could facilitate differentiation and whether histopathologic characteristics could explain the atypical presentation. Methods: We identified 3 neuropathologically-defined ca-MSA patients with clinically diagnosed PSP who underwent various antemortem brain imaging: MRI and PET imaging using 11 C-Pittsburgh compound B, 18 F-flortaucipir, and 18 F-fluorodeoxyglucose. We compared clinical features, brainstem planimetry, and radiotracer standardized uptake value ratios in ca-MSA to 10 autopsy-confirmed PSP patients and 10 healthy controls (imaging only). We also compared histologic count of neuronal loss, iron deposition and α -synuclein-immunoreactive glial cytoplasmic inclusion burden to 10 autopsy-confirmed MSA-parkinsonism (MSA-P) cases. Results: Ca-MSA had better PSP Saccadic Impairment Scale scores ( p = 0.003) and more frequent good levodopa response ( p = 0.061) than PSP. Ca-MSA showed higher midbrain-to-pons ratio and lower Magnetic Resonance Parkinsonism Index than PSP (each, p = 0.036) and exhibited lower glucose metabolism in the putamen and globus pallidus versus PSP ( p = 0.017) and controls ( p = 0.007). These same regions showed higher flortaucipir uptake in ca-MSA than PSP ( p = 0.007 for putamen, p = 0.049 for pallidum) and controls ( p = 0.012). Lower flortaucipir retention was observed in the subthalamic nucleus versus PSP ( p = 0.007). The putamen-to-subthalamic ratio distinguished ca-MSA from PSP. No histopathological differences were observed for ca-MSA versus typical MSA-P. Conclusion: Severity of saccadic impairment, levodopa responsiveness, MRI planimetric measurements, and different patterns of fluorodeoxyglucose and flortaucipir uptake can help improve antemortem differentiation of MSA masquerading as PSP from true PSP. Highlights: Atypical MSA shows eye movement problems and absent-few autonomic symptoms like PSP. MRI biomarkers (midbrain/pons ratio and MRPI) may distinguish atypical MSA from PSP. Lenticular nuclei hypometabolism reflect postmortem atrophy/ α -synuclein pathology. Atypical MSA has higher tau-PET uptake in putamen-pallidum than PSP and controls. High flortaucipir uptake in basal ganglia may be related to iron deposition in MSA.