Clinical Aspects of the Differential Diagnosis of Parkinson's Disease and Parkinsonism

Abstract

Parkinsonism is a clinical syndrome presenting with bradykinesia, tremor, rigidity, and postural instability. Nonmotor symptoms have recently been included in the parkinsonian syndrome, which was traditionally associated with motor symptoms only. Various pathologically distinct and unrelated diseases have the same clinical manifestations as parkinsonism or parkinsonian syndrome. The etiologies of parkinsonism are classified as neurodegenerative diseases related to the accumulation of toxic protein molecules or diseases that are not neurodegenerative. The former class includes Parkinson's disease (PD), multiple-system atrophy, progressive supranuclear palsy, and corticobasal degeneration. Over the past decade, clinical diagnostic criteria have been validated and updated to improve the accuracy of diagnosing these diseases. The latter class of disorders unrelated to neurodegenerative diseases are classified as secondary parkinsonism, and include drug-induced parkinsonism (DIP), vascular parkinsonism, and idiopathic normal-pressure hydrocephalus (iNPH). DIP and iNPH are regarded as reversible and treatable forms of parkinsonism. However, studies have suggested that the absence of protein accumulation in the nervous system as well as managing the underlying causes do not guarantee recovery. Here we review the differential diagnosis of PD and parkinsonism, mainly focusing on the clinical aspects. In addition, we describe recent updates to the clinical criteria of various disorders sharing clinical symptoms with parkinsonism.

Keywords: Parkinson disease, secondary; Parkinson's disease; Parkinson-plus syndromes; Parkinsonian disorders; differential diagnosis.

Fig. 1. Dopamine transporter image in Parkinson’s disease. A: [¹⁸F]-N-3-fluoropropyl-2-betacarboxymethoxy-3-beta-(4-iodophenyl) nortropane positron emission tomography computed tomography in a patient with Parkinson’s disease shows decreased uptake of the dopamine transporter (DAT) in the bilateral putamen, severely on the right side, with an anterior-posterior gradient. B: Normal DAT uptake in the striatum in a healthy subject.

Fig. 2. Brain MRI in Parkinson-plus syndromes. A and B: Brain MRI in a patient with progressive supranuclear palsy shows midbrain atrophy. The arrowhead indicates the hummingbird sign in a sagittal T1-weighted image (A) and the arrow indicates the morning-glory sign in an axial T1-weighted image (B). C and D: Brain MRI in a patient with multiple-system atrophy. C: Cerebellar-pontine atrophy is shown in a T1-weighted sagittal image. D: Atrophy in the middle cerebellar peduncle and the hot-cross-bun sign (arrowhead) are shown in a T2-weighed axial image. E: Brain MRI FLAIR images in a patient with corticobasal syndrome showing severe asymmetric parietofrontal atrophy on the left side.

Fig. 3. Brain MRI in vascular parkinsonism and idiopathic normal pressure hydrocephalus. A: Brain MRI showing multiple ischemic lesions in the bilateral periventricular white matter and basal ganglia in a patient with lower body parkinsonism. B: Brain MRI showing ventriculomegaly with disproportionately enlarged subarachnoid space in coronal views suggesting idiopathic normal hydrocephalus.