Differential diagnosis of Parkinson disease

Category	Disorder	Pathophysiology	Core clinical features	Clues and distinguishing features from PD
Prominent tremor	Essential tremor	Not well characterized	Bilateral action tremor in upper extremities Often also involves head and/or voice	Tremor is not present at rest (unless tremor is severe) No involvement of face or legs Family history Relieved by alcohol
Atypical parkinsonian disorders	Dementia with Lewy bodies	Synucleinopathy	Dementia Visual hallucinations Fluctuating cognition Parkinsonism	Dementia begins before or at the same time as motor symptoms
	Multiple system atrophy	Synucleinopathy; oligodendroglial alpha-synuclein aggregation	Parkinsonism and/or cerebellar dysfunction Autonomic failure Pyramidal signs	Poor response to levodopa Symmetric motor symptoms Early falls Relatively preserved cognitive function Nocturnal stridor
	Progressive supranuclear palsy	Tauopathy; tau-positive deposits in neurons and glia of basal ganglia, brainstem, cerebellum, and cortex	Gait disturbance with falls Ophthalmoparesis Parkinsonism	Poor response to levodopa Early falls No tremor Pseudobulbar affect
	Corticobasal degeneration	Tauopathy; tau-positive deposits in neurons and glia of cortex and striatum	Asymmetric movement disorder (limb rigidity, dystonia, and/or myoclonus) Orobuccal or limb apraxia Cortical sensory deficits Alien limb phenomenon Cognitive dysfunction	Poor response to levodopa Aphasia, apraxia, and cortical sensory loss
Other neurodegenerative disorders	Idiopathic and familial basal ganglia calcification	Calcium deposits in basal ganglia; multiple causative genes	Parkinsonism Chorea Dystonia Cognitive impairment Ataxia	Basal ganglia calcification on CT Family history (autosomal dominant or recessive pattern)
	Huntington disease	CAG repeat expansion in the HTT gene; toxic gain-of-function mechanism due to mutant huntingtin protein	Chorea Psychiatric illness Dementia Parkinsonism more common with older age of onset	Abnormal eye movements Motor impersistence No tremor Family history
	Frontotemporal dementia with parkinsonism	Tauopathy; pathogenic variant in the MAPT gene on chromosome 17	Frontotemporal dementia (usually behavioral variant) Parkinsonism	Family history (autosomal dominant pattern) Younger age of onset Early memory impairment
	Spinocerebellar ataxia	>40 genetic causes	Progressive cerebellar syndrome Variable oculomotor, retinal, pyramidal, extrapyramidal, sensory, and cognitive symptoms depending on gene defect	Younger age of onset Family history
Secondary parkinsonism	Causes	Examples
	Drug-induced	Antipsychotic agents, metoclopramide, prochlorperazine, tetrabenazine, valproic acid
	Vascular	Vascular parkinsonism, vascular dementia
	Toxic	Carbon disulfide, carbon monoxide, cyanide, MPTP, manganese, organic solvents
	Metabolic	Hypoparathyroidism, pseudohypoparathyroidism, chronic liver failure, extrapontine myelinolysis, end-stage kidney disease with diabetes, type 2 diabetes
	Structural	Normal pressure hydrocephalus, chronic subdural hematoma, tumors involving striatonigral circuits, head trauma
	Infectious	Encephalitis lethargica, HIV/AIDS, neurosyphilis, prion disease, progressive multifocal leukoencephalopathy, toxoplasmosis
	Genetic	Wilson disease, neurodegeneration with brain iron accumulation, neuroacanthocytosis

PD: Parkinson disease; CT: computed tomography; CAG: cytosine-adenine-guanine; HTT: huntingtin; MAPT: microtubule associated protein tau; MPTP: 1-methyl-phenyl-1,2,3,6-tetrahydropyridine; HIV: human immunodeficiency virus; AIDS: acquired immunodeficiency syndrome.

Graphic 141072 Version 1.0

خرید پکیج

Differential diagnosis of Parkinson disease