Parkinsonian syndromes

Abstract

Purpose of review: The different parkinsonian conditions can be challenging to separate clinically. This review highlights the important clinical features that guide the diagnosis of Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Strategies for treatment and disease management are also discussed.

Recent findings: Over the past decade there has been an increasing recognition of the broad clinical presentations of the neurodegenerative forms of parkinsonism. Nonmotor symptoms in these diseases, including psychiatric, cognitive, autonomic, and gastrointestinal dysfunction, appear to have a major impact on quality of life and disability. PSP and CBD are now considered pathologic diagnoses, with several different and varied clinical phenotypes, that overlap and share features with PD and frontotemporal dementia syndromes. PD is distinguished by its excellent response to dopaminergic medications that is maintained over many years, in contrast to the response seen in patients with MSA and PSP. New diagnostic criteria have been proposed for CBD. No new therapeutic interventions have emerged for PSP, MSA, or CBD. Infusional therapies and deep brain stimulation surgery are established therapies for advanced PD.

Summary: The "parkinsonian syndromes" encompass a number of nosologic entities that are grouped together on the basis of their shared clinical features but are separated on the basis of their different pathologies. Overall, the consideration of clinical signs, mode of disease onset, and nature of disease progression are all important to make a timely and definitive diagnosis.

Figure 1-1

Sagittal T2-weighted brain MRI of a patient with progressive supranuclear palsy–Richardson syndrome demonstrating substantial atrophy of the midbrain, yielding the “hummingbird sign” (arrow). Associated frontal-predominant atrophy, as demonstrated by thinning of the anterior portion of the corpus callosum and ex vacuo hydrocephalus is also present. Reprinted with permission from Biller J, Espay A, Lippincott Williams & Wilkins. © 2013, Wolters Kluwer Health.

Figure 1-2

Axial T2-weighted brain MRI of a patient with multiple system atrophy–parkinsonism demonstrating a slitlike area of hyperintensity bordered by hypointensity (from iron deposition) in the putamen, worse on the right (arrows). The putaminal atrophy is always greater on the opposite side of the more affected hemibody. Reprinted with permission from Biller J, Espay A, Lippincott Williams & Wilkins. © 2013, Wolters Kluwer Health.

Figure 1-3

Axial fluid-attenuated inversion recovery (FLAIR) brain MRI showing asymmetric hemispheric atrophy, predominantly right parietal, in a patient with corticobasal syndrome due to Alzheimer disease pathology. Reprinted with permission from Biller J, Espay A, Lippincott Williams & Wilkins. © 2013, Wolters Kluwer Health.

Figure 1-4

Axial fluid-attenuated inversion recovery (FLAIR) brain MRI of a patient with vascular parkinsonism demonstrating moderate confluent periventricular and cotton-shaped deep white matter hyperintensities, with associated enlargement of the lateral ventricles and moderate cortical atrophy. Reprinted with permission from Biller J, Espay A, Lippincott Williams & Wilkins. © 2013, Wolters Kluwer Health.

Figure 1-5

The pathologic (progressive supranuclear palsy [PSP], corticobasal degeneration [CBD], frontotemporal lobar degeneration [FTLD]–tau, FTLD–TAR DNA-binding protein [TDP], and Alzheimer disease [AD]), genetic (frontotemporal dementia with parkinsonism-17 [FTDP-17]/FTLD with progranulin mutations [FTLD-PGRN], FTDP-17T/FTLD with microtubule-associated protein tau mutations [FTLD-MAPT]), clinical (bottom), and neuroimaging (top) overlap between motor and cognitive disorders. Classic PSP (green) is predicted by the presence of symmetric parkinsonism and brainstem predominant atrophy, among other features (left end of the diagram; relatively few pathology-proven CBD cases). Conversely, classic CBD (red) can be predicted by a markedly asymmetric parkinsonism with cortical-predominant atrophy (right end of the diagram; relatively few pathology-proven PSP cases). Less characteristic presentations with co-occurrence of behavioral or personality changes or bulbar/pseudobulbar features fall within the spectrum of FTLD (purple)-most often FTLD-tau when PSP-like features are associated, or FTLD-TDP when corticobasal syndrome (CBS)–like or language abnormalities are associated. AD is the most common non-CBD etiology in the CBS spectrum (also right end of the diagram). Modified from Espay AJ,Litvan I, J Mol Neurosci. © 2013 with permission from Springer Science + Business Media. link.springer.com/article/10.1007%2Fs12031-011-9632-1.