Progressive Supranuclear Palsy (PSP) is a 4R-tauopathy characterized by progressive postural instability, vertical supranuclear gaze palsy, and cognitive impairment. Accurate diagnosis remains challenging, particularly in early disease stages, due to clinical overlap with Parkinson's disease (PD), Corticobasal Syndrome (CBS), and other parkinsonian disorders. This page details current diagnostic approaches, including clinical criteria, imaging biomarkers, CSF analysis, and differential diagnosis.
Clinical Diagnostic Criteria
Movement Disorder Society-PSP Criteria (MDS-PSP 2017)
The MDS-PSP criteria represent the current standard for PSP diagnosis, providing four phenotypic subtypes with varying levels of diagnostic certainty:
| Level | Description | |-------|-------------| | Probable PSP | Core clinical features present with no alternative explanation | | Possible PSP | Core or suggestive features present but with some uncertainty | | Suggestive of PSP | Fewer or less specific features, requiring imaging support | | Laboratory-supported PSP | Specific biomarker findings supporting diagnosis |
Core Clinical Features
Vertical supranuclear gaze palsy (VSGP) — Cardinal feature; downward gaze impairment is most specific
Postural instability with falls — Within first year of symptoms predicts PSP-P (parkinsonian variant)
Progressive gait freezing — Early gait ignition failure and freezing
Progressive Supranuclear Palsy (PSP) is a 4R-tauopathy characterized by progressive postural instability, vertical supranuclear gaze palsy, and cognitive impairment. Accurate diagnosis remains challenging, particularly in early disease stages, due to clinical overlap with Parkinson's disease (PD), Corticobasal Syndrome (CBS), and other parkinsonian disorders. This page details current diagnostic approaches, including clinical criteria, imaging biomarkers, CSF analysis, and differential diagnosis.
Clinical Diagnostic Criteria
Movement Disorder Society-PSP Criteria (MDS-PSP 2017)
The MDS-PSP criteria represent the current standard for PSP diagnosis, providing four phenotypic subtypes with varying levels of diagnostic certainty:
| Level | Description | |-------|-------------| | Probable PSP | Core clinical features present with no alternative explanation | | Possible PSP | Core or suggestive features present but with some uncertainty | | Suggestive of PSP | Fewer or less specific features, requiring imaging support | | Laboratory-supported PSP | Specific biomarker findings supporting diagnosis |
Core Clinical Features
Vertical supranuclear gaze palsy (VSGP) — Cardinal feature; downward gaze impairment is most specific
Postural instability with falls — Within first year of symptoms predicts PSP-P (parkinsonian variant)
Progressive gait freezing — Early gait ignition failure and freezing
F-18 AV-1451 (Flortaucipir): Binds to paired helical filament tau
Preliminary findings: Elevated binding in PSP brainstem and subcortical structures
Clinical utility: Currently research use only
CSF Biomarkers
Established Markers
| Biomarker | PSP Finding | Clinical Utility | |-----------|-------------|------------------| | [Neurofilament light](/biomarkers/neurofilament-light-chain-nfl) chain (NfL) | Elevated | High sensitivity for neurodegeneration | | Total tau (t-tau) | Normal to mildly elevated | Differentiates from AD | | Phosphorylated tau (p-tau) | Normal or mildly elevated | Distinguishes from AD | | [Alpha-synuclein](/proteins/alpha-synuclein) | Normal | Rules out MSA-P, PD | | [Beta-amyloid](/proteins/amyloid-beta) 1-42 | Normal | Rules out AD comorbidity |
Emerging Biomarkers
Tau oligomers: Elevated in PSP vs. controls
Neurogranin: Marker of synaptic dysfunction
YKL-40 (Chitinase-3-like protein 1): Astrocytic activation marker