Is there a Progressive Supranuclear Palsy (PSP) or Corticobasal Syndrome (CBS) variant that perfectly mimics Multiple System Atrophy (MSA)?

PSP and CBS Variants That Mimic MSA

While there is no PSP or CBS variant that perfectly mimics MSA, certain clinical presentations of PSP and CBS can overlap with MSA features, making differential diagnosis challenging. 1

Pathophysiological Distinctions

The fundamental distinction between these disorders lies in their underlying pathology:

• MSA: A synucleinopathy with abnormal cytoplasmic inclusions of ubiquitin and alpha-synuclein in oligodendroglia 1
• PSP and CBS: Tauopathies with abnormal tau protein accumulation in different brain regions 1

Overlapping Clinical Presentations

PSP Variants That Can Mimic MSA

1. PSP-Parkinsonism (PSP-P)

   • Features resembling MSA:
     • Parkinsonism responsive to levodopa (in 30% of PSP cases) 2
     • Longer diagnostic latency than classic Richardson syndrome 3
     • More benign clinical trajectory 3

2. PSP-Subcortical Variants

   • Can present with features that overlap with MSA:
     • Progressive gait freezing 3
     • Falls (occurs in both disorders) 1, 4
     • Pyramidal involvement 2

3. PSP-CBS Hybrid Presentations

   • Shows imaging features of both disorders with volume loss in:
     • Brainstem (superior cerebellar peduncle) - typical of PSP
     • Cortical regions (medial/lateral premotor, prefrontal and motor cortex) - typical of CBS 5

CBS Features That Can Overlap with MSA

• Ataxia and apraxia (found in 50% of PSP patients) 2
• Asymmetric limb rigidity and dystonia 1
• Cognitive impairment 1

Key Distinguishing Features

Features More Suggestive of MSA

1. Dysautonomia

   • Present early in MSA (46% within first year of motor symptoms)
   • Can precede motor symptoms by up to 3 years
   • Note: 15% of pathologically confirmed MSA cases did not have dysautonomia in life 2

2. Clinical Subtypes

   • MSA-P: Predominant parkinsonian features (striatonigral degeneration)
   • MSA-C: Predominant cerebellar features (olivopontocerebellar atrophy)
   • MSA-A: Predominant autonomic features (Shy-Drager syndrome) 1

Features More Suggestive of PSP

1. Vertical Supranuclear Gaze Palsy

   • Classic finding, though usually appears later in disease course
   • The latency of down-gaze palsy correlates with disease progression 2

2. Early Falls

   • Occur earlier in PSP than MSA 4
   • Lurching gait and axial dystonia 1

3. Cognitive Impairment

   • Occurs earlier in PSP than MSA 4
   • Frontal cognitive dysfunction 6

Diagnostic Approach

1. Clinical Evaluation

   • Assess for vertical gaze palsy (especially downward)
   • Evaluate for early autonomic dysfunction (suggestive of MSA)
   • Document fall patterns and timing
   • Test for levodopa responsiveness

2. Neuroimaging

   • MRI is preferred over CT 1
   • Look for specific patterns:
     • MSA: Putaminal atrophy, "hot cross bun" sign in pons
     • PSP: Midbrain atrophy ("hummingbird" sign) - common in all PSP variants 3
     • CBS: Asymmetric frontoparietal atrophy

3. Biomarkers

   • Serum neurofilament light chain (NF-L) levels can help distinguish PD from PSP and CBS 3

Pitfalls in Diagnosis

1. Misdiagnosis is Common

   • 30% of pathologically confirmed PSP cases were incorrectly diagnosed antemortem (all lacking down-gaze palsy) 2
   • 23% of pathologically confirmed MSA cases were incorrectly diagnosed 2

2. Overlapping Features

   • Falls in the first year, pyramidal involvement, and freezing of gait can occur in both PSP and MSA 2
   • Some PSP patients (30%) may show levodopa responsiveness, especially those with resting tremor 2

3. Atypical Presentations

   • Nearly half (48.5%) of PSP patients do not have the classic Richardson syndrome subtype 3
   • Some MSA patients (15%) may not develop autonomic symptoms during their lifetime 2

The diagnostic challenge is significant, but careful attention to the timing and progression of symptoms, particularly the development of vertical gaze palsy in PSP and early autonomic dysfunction in MSA, can help differentiate these disorders.