Journal Article

Upper motor neuron‐predominant motor neuron disease presenting as atypical parkinsonism: A clinicopathological study

White, Adrianna E., Bieniek, Kevin F., Dickson, Dennis W., DeJesus‐Hernandez, Mariely, Finch, NiCole A., Blitterswijk, Marka, Murakami, Aya, Fujioka, Shinsuke, Koga, Shunsuke, Sekiya, Hiroaki, Nakamura, Masataka, Wszolek, Zbigniew K., Murray, Melissa E., Tsuboi, Yoshio

2025

Overview

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by upper and lower motor neuron signs. There are, however, cases where upper motor neurons (UMNs) are predominantly affected, leading to clinical presentations of UMN‐dominant ALS or primary lateral sclerosis. Furthermore, cases exhibiting an UMN‐predominant pattern of motor neuron disease (MND) presenting with corticobasal syndrome (CBS) have been sparsely reported. This study aims to clarify the clinicopathological features of patients with UMN‐predominant MND. We reviewed 24 patients with UMN‐predominant MND with TDP‐43 pathology in the presence or absence of frontotemporal lobar degeneration. Additionally, we reviewed the medical records of patients with pathologically‐confirmed corticobasal degeneration (CBD) who received a final clinical diagnosis of CBS (n = 10) and patients with pathologically‐confirmed progressive supranuclear palsy (PSP) who received a final clinical diagnosis of PSP syndrome (n = 10). Of 24 UMN‐predominant MND patients, 20 had a clinical diagnosis of an atypical parkinsonian disorder, including CBS (n = 11) and PSP syndrome (n = 8). Only two patients had antemortem diagnoses of motor neuron disease. UMN‐predominant MND patients with CBS less frequently exhibited apraxia than those with CBD, and they were less likely to meet clinical criteria for possible or probable CBS. Similarly, UMN‐predominant MND patients with PSP syndrome less often met clinical criteria for probable PSP than PSP patients with PSP syndrome. Our findings suggest that UMN‐predominant MND can mimic atypical parkinsonism, and should be considered in the differential diagnosis of CBS and PSP syndrome, in particular when criteria are not met. Heatmap and hierarchical clustering based on neuronal loss in 24 UMN‐predominant MND cases. Two distinct clusters are identified by hierarchical clustering based on neuronal loss. The heatmap reflects the severity of neuronal loss, and a color scale is given at the right. Missing data are shown in gray. Patients are represented with columns, and the study ID of each patient is provided. The main clinical features and diagnoses of each case are shown.

• Publisher: John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Aged / Aged, 80 and over / Amyotrophic lateral sclerosis / Amyotrophic Lateral Sclerosis - diagnosis / Amyotrophic Lateral Sclerosis - pathology / atypical parkinsonism / Basal ganglia / Central nervous system diseases / Cognitive ability / Corticobasal Degeneration - diagnosis / Corticobasal Degeneration - pathology / Criteria / Degeneration / Diagnosis / Diagnosis, Differential / Differential diagnosis / DNA-Binding Proteins - metabolism / Female / Frontotemporal dementia / Humans / Male / Medical records / Middle Aged / Motor Neuron Disease - diagnosis / Motor Neuron Disease - pathology / Motor neuron diseases / Motor neurone disease / Motor Neurons - pathology / Movement disorders / Neurodegeneration / Neurodegenerative diseases / Parkinsonian Disorders - diagnosis / Parkinsonian Disorders - pathology / Patients / Progressive supranuclear palsy / Supranuclear Palsy, Progressive - diagnosis / Supranuclear Palsy, Progressive - pathology / TDP‐43 / upper‐motor‐neuron‐predominant motor neuron disease