How to differentiate multiple system atrophy (MSA) and progressive supranuclear palsy (PSP) in a geriatric patient based on symptoms and signs?

Differentiating Multiple System Atrophy from Progressive Supranuclear Palsy: Top 15 Clinical Features

The most reliable clinical features to distinguish PSP from MSA are vertical supranuclear gaze palsy (especially downward), early severe falls within the first year, and axial-predominant rigidity for PSP, versus prominent early autonomic dysfunction (urinary incontinence, orthostatic hypotension), cerebellar ataxia, and preserved eye movements for MSA. 1, 2

Age and Disease Onset

• PSP: Typical onset in the sixth or seventh decade with mean age of 63 years 1
• MSA: Typical onset between 55-65 years of age 1
• Clinical Pearl: PSP patients tend to present slightly older than MSA patients, though there is significant overlap 2

Cardinal Distinguishing Features

Features Strongly Favoring PSP:

1. Vertical supranuclear gaze palsy (especially downward gaze): This is the hallmark feature of PSP, though it typically appears later in the disease course; early ocular symptoms include blurred vision and slow saccades 1, 3, 2

2. Early severe postural instability and falls: Unexplained falls within the first year of symptom onset, often presenting as a "lurching gait" with axial dystonia 1, 2

3. Axial-predominant rigidity: Rigidity affects axial muscles more than limbs, distinguishing it from MSA 3

4. Absence of tremor: Tremor is uncommon in PSP 4, 2

5. Poor or absent levodopa response: PSP patients typically show minimal response to dopaminergic therapy 2

Features Strongly Favoring MSA:

1. Prominent early autonomic dysfunction: Urinary incontinence, orthostatic hypotension, and constipation are significantly more common and severe in MSA 1, 4

2. Cerebellar ataxia: Particularly prominent in MSA-C subtype, but cerebellar signs frequently occur in MSA-P as well 1, 5

3. Dyskinesia: Significantly higher incidence in MSA-P patients compared to PSP 4

4. Preserved or mildly impaired eye movements: MSA typically shows excessive square-wave jerks, mild hypometria of saccades, and impaired vestibular-ocular reflex, but NOT vertical gaze palsy 5

5. Pyramidal signs: Frequently reported in MSA but not characteristic of PSP 1

Cognitive and Behavioral Differences

1. Cognitive impairment severity: PSP patients demonstrate significantly more severe cognitive deficits than MSA-P patients 4

• MMSE cut-off: Score ≤24.5 suggests PSP over MSA-P 4
• MoCA cut-off: Score ≤20.5 suggests PSP over MSA-P 4

1. Executive dysfunction: More prominent and severe in PSP, associated with frontal lobe involvement 6

Additional Distinguishing Features

1. Blepharospasm: More common in MSA than PSP 5

2. Salivation problems: Higher incidence in PSP patients 4

3. Disease progression rate: Mean disease duration in MSA is approximately 6 years; both conditions progress more rapidly than idiopathic Parkinson's disease 1, 7

Pathophysiological Distinction

• PSP: A tauopathy with abnormal tau protein accumulation 1
• MSA: A synucleinopathy with alpha-synuclein accumulation in oligodendroglia (not neurons) 1, 8

Clinical Algorithm for Differentiation

Step 1 - Assess Eye Movements:

• Vertical supranuclear gaze palsy (especially downward) → Strongly suggests PSP 1, 3, 2
• Preserved vertical gaze with square-wave jerks → Favors MSA 5

Step 2 - Evaluate Fall History:

• Severe falls within first year with lurching gait → Strongly suggests PSP 1, 2
• Falls present but not as prominent early feature → Consider MSA 4

Step 3 - Assess Autonomic Function:

• Early severe urinary incontinence, orthostatic hypotension → Strongly suggests MSA 1, 4
• Mild or late autonomic symptoms → Favors PSP 1

Step 4 - Check for Cerebellar Signs:

• Prominent ataxia, dysmetria, intention tremor → Strongly suggests MSA 1, 5
• Absent cerebellar signs → Favors PSP 1

Step 5 - Cognitive Assessment:

• MMSE ≤24.5 or MoCA ≤20.5 with prominent executive dysfunction → Favors PSP 4, 6
• Better preserved cognition (MMSE >24.5, MoCA >20.5) → Favors MSA 4

Critical Pitfalls to Avoid

• Do not wait for vertical gaze palsy to diagnose PSP: Early ocular symptoms include blurred vision and slow saccades; the classic vertical supranuclear gaze palsy usually appears later in the disease course 1

• Do not dismiss early falls: Unexplained falls within the first year are highly specific for PSP and should prompt careful evaluation for vertical gaze abnormalities 2

• Do not overlook autonomic symptoms: Early severe dysautonomia (especially urinary incontinence requiring catheterization) strongly suggests MSA over PSP 1, 4

• Recognize that both conditions can present with parkinsonism: Both PSP and MSA demonstrate bradykinesia and rigidity; the distinguishing features are the "plus" symptoms 1

• Imaging is essential but not definitive: MRI showing midbrain atrophy (especially superior cerebellar peduncle) suggests PSP, while pontine and cerebellar atrophy suggests MSA, but clinical diagnosis remains challenging 1, 6

• Levodopa response is not reliable alone: While poor levodopa response is common in both conditions, PSP typically shows even less response than MSA 2