What are the main differences between all types of atypical parkinsonism, including Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), and Corticobasal Degeneration (CBD)?

Main Differences Between Atypical Parkinsonism Types

The main differences between atypical parkinsonism syndromes (Progressive Supranuclear Palsy, Multiple System Atrophy, and Corticobasal Degeneration) are defined by their distinct clinical presentations, pathological findings, and progression patterns, with PSP characterized by postural instability and supranuclear gaze palsy, MSA by prominent autonomic dysfunction, and CBD by asymmetric cortical sensorimotor deficits. 1, 2, 3

Progressive Supranuclear Palsy (PSP)

• PSP syndrome (Richardson's syndrome) is characterized by postural instability and supranuclear gaze palsy, with varying degrees of cognitive, behavioral, or other movement symptoms 1
• Key diagnostic features include:
  • Early falls (a significant red flag for diagnosis) 4
  • Vertical supranuclear gaze palsy (particularly downward gaze) 1, 5
  • Impaired optokinetic nystagmus (OKN) 5
• Pathologically, PSP is typically associated with frontotemporal lobar degeneration (FTLD-PSP), a tauopathy 1
• Midbrain tegmentum atrophy on MRI is significantly more common in PSP than in other parkinsonian syndromes 5

Multiple System Atrophy (MSA)

• MSA is classified into three clinical subtypes: MSA-P (parkinsonism predominant), MSA-C (cerebellar predominant), and MSA-A (autonomic predominant/Shy-Drager syndrome) 2, 3
• Distinctive clinical features include:
  • Prominent autonomic dysfunction (83% have urinary dysfunction and 75% have symptomatic orthostatic hypotension) 2
  • Parkinsonism with poor levodopa response (present in 87% of cases) 2
  • Cerebellar ataxia (present in 64% of patients) 2
• MSA is a synucleinopathy characterized by glial cytoplasmic inclusions (GCIs) containing misfolded α-synuclein 2, 4
• Shorter disease duration (approximately 6 years from diagnosis) compared to typical Parkinson's disease 2

Corticobasal Degeneration (CBD)

• Corticobasal syndrome presents with cortical sensorimotor deficits and cognitive difficulties with asymmetric rigidity and motor dysfunction 1
• Distinctive features include:
  • Limb apraxia (difficulty planning or performing learned motor tasks) 1
  • Asymmetric rigidity and dystonia 1, 4
  • Executive dysfunction 1
• Pathologically, CBD is most often associated with FTLD-CBD (a tauopathy), but can sometimes be caused by other pathologies including AD, FTLD-PSP, or FTLD-Pick's 1

Key Differential Features

• Response to levodopa: All atypical parkinsonisms typically show poor response to levodopa therapy, in contrast to Parkinson's disease 2, 6
• Autonomic dysfunction: Most prominent in MSA, less severe in PSP and CBD 2, 3
• Cognitive impairment: More prominent in PSP and CBD than in MSA 3
• Imaging findings:
  • PSP: Midbrain atrophy ("hummingbird" or "penguin" sign) 5
  • MSA: Putaminal, pontine, and cerebellar atrophy with characteristic "hot cross bun" sign in pons 2
  • CBD: Asymmetric cortical atrophy 4
• Biomarkers:
  • Normal cardiac MIBG scintigraphy (H/M ratio) in PSP, CBD, and early MSA, unlike in Parkinson's disease which shows decreased uptake as disease progresses 5

Pathological Classification

• PSP and CBD are tauopathies (tau protein accumulation) 1
• MSA is a synucleinopathy (α-synuclein accumulation), similar to Parkinson's disease but with different distribution patterns 2, 4

Disease Progression and Prognosis

• MSA typically has a more rapid progression with shorter survival (approximately 6 years from diagnosis) 2
• PSP also has relatively rapid progression compared to Parkinson's disease 4
• All atypical parkinsonisms have significant impacts on quality of life and higher mortality rates than Parkinson's disease 3

Diagnostic Challenges

• Significant overlap in symptoms, especially in early stages, makes differential diagnosis challenging 7, 4
• Expanding phenotypic spectrum of these disorders further complicates early diagnosis 7
• Clinical features may evolve over time, requiring reassessment of diagnosis 4