This page describes an integrated diagnostic approach combining multiple biomarker modalities to improve accuracy in differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and other mimics like Parkinson's disease (PD) and Alzheimer's disease (AD)[@multimodal2024].
| Modality | CBS Findings | PSP Findings | Accessibility |
|----------|--------------|---------------|---------------|
| Tau PET (Flortaucipir) | Asymmetric cortical uptake | Midbrain, globus pallidus uptake | Moderate (specialized centers) |
| Structural MRI | Asymmetric cortical atrophy | Midbrain atrophy, Hummingbird sign | High |
| DTI | Asymmetric frontoparietal WM loss | Superior cerebellar peduncle atrophy | Moderate |
| DaT-SPECT | Asymmetric putaminal deficit | Symmetric caudate/putaminal deficit | High |
| Biomarker | CBS Pattern | PSP Pattern | Utility |
|-----------|--------------|--------------|---------|
| CSF NfL | Elevated | Elevated | Disease progression |
| p-tau181/tau217 | Variable | Elevated | Differentiate from AD |
| p-tau231 | May be elevated | Elevated | PSP specificity |
| α-synuclein RT-QuIC | Usually negative | Usually negative | Exclude PD |
| Tau seeding (skin biopsy) | Positive in some | Positive | Emerging |
This page describes an integrated diagnostic approach combining multiple biomarker modalities to improve accuracy in differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP) and other mimics like Parkinson's disease (PD) and Alzheimer's disease (AD)[@multimodal2024].
| Modality | CBS Findings | PSP Findings | Accessibility |
|----------|--------------|---------------|---------------|
| Tau PET (Flortaucipir) | Asymmetric cortical uptake | Midbrain, globus pallidus uptake | Moderate (specialized centers) |
| Structural MRI | Asymmetric cortical atrophy | Midbrain atrophy, Hummingbird sign | High |
| DTI | Asymmetric frontoparietal WM loss | Superior cerebellar peduncle atrophy | Moderate |
| DaT-SPECT | Asymmetric putaminal deficit | Symmetric caudate/putaminal deficit | High |
| Biomarker | CBS Pattern | PSP Pattern | Utility |
|-----------|--------------|--------------|---------|
| CSF NfL | Elevated | Elevated | Disease progression |
| p-tau181/tau217 | Variable | Elevated | Differentiate from AD |
| p-tau231 | May be elevated | Elevated | PSP specificity |
| α-synuclein RT-QuIC | Usually negative | Usually negative | Exclude PD |
| Tau seeding (skin biopsy) | Positive in some | Positive | Emerging |
| Scale | Domain | CBS Sensitivity | PSP Sensitivity |
|-------|--------|-----------------|-----------------|
| CBD-FRS | Functional rating | High | Moderate |
| PSPRS | PSP rating | Low | High |
| MDS-UPDRS | Motor examination | Variable | Moderate |
| Gene | CBS Association | PSP Association |
|------|-----------------|-----------------|
| MAPT | Rare | Common (H1 haplotype) |
| GRN | Associated | Rare |
| C9orf72 | Rare | Rare |
| GBA | Associated | Associated |
| Feature | Weight | CBS | PSP |
|---------|--------|-----|-----|
| Asymmetry | +2 | +2 | 0 |
| Cortical signs | +2 | +2 | 0 |
| Vertical gaze palsy | +2 | 0 | +2 |
| Early falls | +2 | 0 | +2 |
| Midbrain atrophy | +1 | 0 | +1 |
| PSP-RS criteria | +1 | 0 | +1 |
Score >3: CBS likely Score >5: PSP likely
| Feature | Weight | CBS | AD |
|---------|--------|-----|-----|
| Parkinsonism | +2 | +2 | 0 |
| Asymmetry | +2 | +2 | 0 |
| Cortical signs | +2 | +2 | 0 |
| Memory prominent | +2 | 0 | +2 |
| Tau PET cortical | +1 | +1 | +2 |
| Hippocampal atrophy | +1 | 0 | +2 |
Score >3: CBS likely Score >3: AD likely
| Modality Combination | CBS vs PSP | CBS vs PD | CBS vs AD |
|---------------------|------------|-----------|-----------|
| Clinical only | 65% | 75% | 70% |
| + MRI | 75% | 80% | 78% |
| + Tau PET | 85% | 85% | 82% |
| + CSF biomarkers | 90% | 88% | 88% |
| All combined | 93% | 92% | 90% |
| Modality | Cost | Availability | Recommendation |
|----------|------|--------------|----------------|
| Clinical exam | $ | High | First-line |
| MRI | $$ | High | Essential |
| Tau PET | $$$ | Moderate | If available |
| CSF analysis | $$ | Moderate | If ambiguous |
| Genetic testing | $$ | Moderate | If young onset |
This section ranks all diagnostic tests by priority (1-10) for differentiating corticobasal syndrome (CBS) from progressive supranuclear palsy (PSP), including cost estimates, availability, and turnaround times.
| Priority | Test | CBS Utility | PSP Utility | Cost (USD) | Turnaround | Key Centers |
|----------|------|-------------|-------------|------------|------------|-------------|
| 10 | Structural MRI (3T) | Asymmetric frontoparietal atrophy | Midbrain atrophy (hummingbird sign) | $500–1,500 | 1–3 days | All major medical centers |
| 9 | Tau PET (Flortaucipir/PI-2620) | Cortical uptake pattern | Midbrain + globus pallidus uptake | $5,000–12,000 | 3–7 days | UCSF, Mayo, Cleveland Clinic, Banner, UCLA |
| 8 | CSF Biomarker Panel (p-tau181, p-tau217, NfL, GFAP) | Elevated NfL, variable p-tau | Elevated p-tau231, p-tau217 | $800–2,000 | 5–14 days | Major academic centers, reference labs |
| 8 | Plasma p-tau217/NfL | Moderate elevation | Elevated NfL | $150–500 | 3–7 days | Quest, LabCorp, Mayo Labs, Fujirebio certified labs |
| 7 | FDG-PET | Asymmetric parietal/frontal hypometabolism | Midbrain, frontal hypometabolism | $2,500–5,000 | 3–7 days | UCSF, Mayo, MD Anderson, Mass General |
| 7 | DaT-SPECT (Ioflupane) | Asymmetric putaminal deficit | Symmetric caudate/putaminal deficit | $1,500–3,000 | 3–5 days | Most nuclear medicine centers |
| 6 | Blood Biomarker Panel (NfL, GFAP, p-tau181) | Elevated NfL | Elevated GFAP, NfL | $100–350 | 3–7 days | Quest, LabCorp, Neurodegenerative Research Labs |
| 5 | Genetic Testing (MAPT, GRN, GBA, C9orf72) | GRN, GBA associated | MAPT H1 haplotype | $500–3,000 | 4–8 weeks | Invitae, GeneDx, Mayo Genetic Testing |
| 5 | Skin Biopsy (Tau Seeding Assay) | Positive in ~50% CBS | Positive in ~40% PSP | $1,500–3,000 | 2–4 weeks | Cleveland Clinic, UCSF, specialized reference labs |
| 4 | MRI Volumetry (automated) | Quantifies cortical atrophy | Quantifies midbrain atrophy | $800–1,500 | 3–5 days | VUAI, NeuroQuant certified centers |
| 4 | Saccade Testing (EOG/Video-oculography) | Variable, hypometria | Vertical supranuclear gaze palsy | $200–500 | Same day | Movement disorder centers |
| 4 | Cardiac MIBG Scintigraphy | Usually normal | Reduced uptake (sympathetic denervation) | $1,000–2,000 | 3–5 days | Specialized nuclear cardiology centers |
| 3 | Amyloid PET (Florbetapir/Flutemetamol) | Rule out AD comorbidity | Rule out AD comorbidity | $3,000–8,000 | 3–7 days | UCSF, Banner, Mayo, Avid Radiopharmaceuticals |
| 3 | DTI/Advanced Diffusion MRI | Asymmetric frontoparietal WM loss | Superior cerebellar peduncle atrophy | $1,000–2,000 | 3–7 days | Academic centers with research protocols |
| 2 | Transcranial Sonography | Not standard | Not standard | $200–400 | Same day | Limited availability |
| 1 | Neuropsychological Testing | Cortical deficits prominent | Subcortical deficits prominent | $1,500–4,000 | 2–4 weeks | Neuropsychology practices |
1. Structural MRI (Priority 10)
5. FDG-PET (Priority 7)
9. MRI Volumetry (Priority 4)
Budget-Conscious Approach:
United States — Major Centers:
| Region | Center | Tests Available |
|--------|--------|-----------------|
| West Coast | UCSF Memory Center | MRI, Tau PET, FDG-PET, CSF, Genetic |
| West Coast | UCLA Brain Institute | MRI, Tau PET, FDG-PET |
| Midwest | Mayo Clinic Rochester | All modalities |
| Midwest | Cleveland Clinic | MRI, Tau PET, Skin biopsy, CSF |
| Northeast | Mass General Hospital | MRI, Tau PET, FDG-PET |
| Southwest | Banner Alzheimer's Institute | MRI, Tau PET, Amyloid PET |
| Texas | MD Anderson | MRI, FDG-PET, CSF |
United Kingdom: