Clinical: asymmetric bradykinesia, rigidity and/or resting tremor; usually a sustained dopaminergic response. Hyposmia, constipation, REM sleep behavior disorder and autonomic symptoms may precede motor disease.

MRI: often normal or nonspecific early. SWI/T2* may show loss of nigrosome-1 (the swallow-tail sign).

Nigrosome-1 loss supports nigrostriatal degeneration but is not specific for PD.

PDD: dementia generally begins more than one year after established motor PD. DLB: dementia precedes or begins within about one year of parkinsonism.

• Relative medial temporal preservation versus typical Alzheimer disease
• Occipital hypometabolism with cingulate island sign on FDG-PET
• Reduced striatal uptake on dopamine transporter imaging

These findings are supportive, not independently diagnostic.

MSA-P: poorly sustained levodopa response, early autonomic failure, dysarthria or postural instability. MSA-C: cerebellar ataxia with autonomic dysfunction.

• Posterior putaminal atrophy, susceptibility and increased diffusivity
• Pontocerebellar and middle cerebellar peduncle atrophy
• MCP T2 hyperintensity and hot cross bun sign

An isolated hyperintense putaminal rim is insufficiently specific, particularly at 3 T.

Peripheral autonomic α-synucleinopathy without established central motor or cognitive involvement. It may precede PD, DLB or MSA; MRI is usually nondiagnostic before central disease develops.

4R tau. Classic PSP-Richardson syndrome features axial rigidity, early falls, slowed vertical saccades or vertical gaze palsy, dysarthria and dysphagia.

• Disproportionate midbrain atrophy
• Hummingbird/penguin and morning glory signs
• Superior cerebellar peduncle atrophy
• Increased MR Parkinsonism Index

Absence of midbrain atrophy does not exclude early or variant PSP.

4R tau. CBD is a pathologic diagnosis. Its classic phenotype is corticobasal syndrome (CBS): asymmetric rigidity/akinesia plus apraxia, cortical sensory loss or alien limb.

• Asymmetric perirolandic and frontoparietal atrophy
• Possible asymmetric basal ganglia atrophy
• Often greater contralateral to affected limbs

CBS ≠ CBD. CBS can reflect CBD, PSP, Alzheimer disease, FTLD-TDP or other pathology.

MAPT-associated disease may cause frontal/anterior temporal atrophy, parkinsonism and PSP-like or corticobasal features. Pick disease is predominantly 3R tau; globular glial tauopathy is a rare 4R disorder. Alzheimer disease contains amyloid-β and mixed 3R/4R tau and may underlie CBS.

GRN- and C9orf72-associated FTD are typically TDP-43 proteinopathies, not tauopathies.

FTLD-TDP may cause behavioral or cognitive dysfunction with parkinsonism or CBS. Hereditary syndromes may combine parkinsonism with spasticity, dystonia or cognitive impairment; integrate imaging with phenotype and molecular diagnosis.

Juvenile Huntington disease may be akinetic-rigid; caudate atrophy is characteristic. Rapidly progressive prion disease may include rigidity or parkinsonism, with cortical and/or deep gray restricted diffusion.

• PKAN (PANK2): pallidal iron with central T2 hyperintensity—eye-of-the-tiger sign
• PLAN (PLA2G6): variable pallidal/nigral iron, cerebellar atrophy and callosal changes
• BPAN (WDR45): nigral/pallidal iron and T1 hyperintense nigral halo
• Neuroferritinopathy: basal ganglia iron with possible cavitation
• Aceruloplasminemia: widespread deep gray, red nucleus and dentate iron

Onset is young, progression is unusually rapid, family history is strong, or MRI shows marked iron, restricted diffusion, white matter disease, calcification or an unexpected atrophy pattern.