Diagnostic Approach to Atypical Parkinsonian Syndromes

Abstract

Purpose of review: Although increasingly recognized, atypical parkinsonian syndromes remain challenging to diagnose and are underrecognized due to overlap with other parkinsonisms. This article provides a diagnostic approach to atypical parkinsonian syndromes, including progressive supranuclear palsy (PSP), multiple system atrophy (MSA), corticobasal degeneration (CBD), and dementia with Lewy bodies. The goal of this review is to aid the clinician in recognizing key clinical and pathologic features and to raise awareness of recent advances in diagnostics and treatment.

Recent findings: Diagnostic criteria for atypical parkinsonian syndromes are evolving to encompass increasingly recognized heterogeneity in the presentation of these disorders and information gleamed from clinicopathologic correlations. PSP and CBD in particular now share similar pathologic clinical features and include a number of phenotypic variants. Pathologic diagnoses are increasingly used in clinical practice, and there is frequent reference now by clinicians to tauopathies, including PSP and CBD, and the synucleinopathies, which include MSA and dementia with Lewy bodies (as well as Parkinson disease). Research into biomarkers, including both tissue and imaging modalities and genetics, has the potential to increase disease recognition and make earlier diagnosis and treatment possible. Although novel therapeutics are being studied for atypical parkinsonian syndromes such as PSP, no new breakthrough interventions have emerged for the treatment of PSP, CBD, and MSA. Current therapeutic management for these disorders frequently uses a multidisciplinary team approach.

Summary: The approach to atypical parkinsonian syndromes requires recognition of a constellation of overlapping but distinct clinical features that help with identifying and distinguishing them from Parkinson disease and other similar disorders.

Figure 5-1

Overlap of parkinsonian syndromes. Atypical parkinsonisms have common features with Parkinson disease, secondary parkinsonisms, and heredodegenerative disorders with parkinsonism.

Figure 5-2

Clinicopathologic overlap of neurodegenerative proteinopathies. Atypical parkinsonian syndromes share abnormal accumulation of proteins such as α-synuclein, tau, amyloid, and TDP-43. ALS = amyotrophic lateral sclerosis; FTD = frontotemporal dementia; FTLD-U = frontotemporal lobar degeneration with ubiquitin; MND = motor neuron disease; TDP-43 = TAR DNA binding protein 43.

Figure 5-3

Typical neuropathologic findings in progressive supranuclear palsy. The macroscopic photo shows atrophy of the superior cerebellar peduncle (SCP) and midbrain structures including the subthalamic nucleus (STN) and loss of pigmented cells in the substantia nigra (SN) (A).The photomicrographs show classic pathologic findings including neurofibrillary tangles (B), neuropil threads (C, arrows), coiled bodies (D), and tufted astrocyte (E, arrow) stained with PHF1 antibody to human tau. Panel A is reprinted with permission from Dickson DW, et al, Curr Opin Neurol. © 2010 Lippincott Williams & Wilkins, Inc. journals.lww.com/co-neurology/Abstract/2010/08000/Neuropathology_of_variants_of_progressive.9.aspx.

Figure 5-4

Sagittal T1-weighted MRI of a patient with progressive supranuclear palsy–Richardson syndrome. Marked midbrain atrophy is present, suggesting the appearance of a hummingbird or penguin sign. Inset shows atrophy of the superior cerebellar peduncles (arrows).

Figure 5-5

Glial cytoplasmic inclusions in multiple system atrophy. Oligodendroglial cytoplasmic inclusions here are stained with antibody to human α-synuclein.

Figure 5-6

Axial T2-weighted MRI of a patient with multiple system atrophy–parkinsonian type demonstrating slitlike hyperintensity (A, arrows) at the rim of the right putamen, fluid-attenuated inversion recovery (FLAIR) hypointensity of posterior putamen (B, arrows), and typical hot cross bun sign representing atrophy and gliosis of the pons (C).

Figure 5-7

Typical Lewy bodies are found in the pigmented cells of the substantial nigra in both Parkinson disease and dementia with Lewy bodies. Here Lewy bodies (arrows) are stained with an antibody specific to the pathologic phosphorylated form (serine 129) of α-synuclein found enriched in Lewy bodies. They have a characteristic round appearance with lighter core and dark halo.