What are the typical symptoms of Multiple System Atrophy (MSA)?

Typical Symptoms of Multiple System Atrophy (MSA)

Multiple System Atrophy (MSA) is characterized by a combination of parkinsonian, autonomic, cerebellar, and pyramidal signs that typically present in adults between 55-65 years of age with rapid progression of disability.

Clinical Presentation by System

Autonomic Dysfunction

• Autonomic symptoms are initial features in 41% of patients and eventually develop in 97% of cases 1
• Common manifestations include:
  • Orthostatic hypotension (present in 68% of patients, severe in 15%) 1
  • Urogenital dysfunction:
    • Men: Erectile dysfunction (often the earliest autonomic symptom) 2
    • Women: Urinary incontinence 1
  • Bladder dysfunction: Urinary retention, incontinence (very common) 3
  • Gastrointestinal symptoms: Constipation, alternating diarrhea and constipation 4

Motor Symptoms

• Parkinsonian features (present in 91% of patients, initial feature in 46%) 1:

  • Akinesia and rigidity (predominant)
  • Asymmetric presentation (74% of cases)
  • Rest tremor (29% of patients, but classical pill-rolling tremor in only 9%)
  • Poor or unsustained response to levodopa (only 13% maintain good response) 1

• Cerebellar symptoms (develop in 52% of patients, initial feature in 5%) 1:

  • Ataxic gait
  • Dysarthria (slurred speech)
  • Limb ataxia
  • Nystagmus

• Pyramidal signs (present in 61% of patients) 1:

  • Hyperreflexia
  • Extensor plantar responses
  • Spasticity

Sleep Disorders

• REM sleep behavior disorder (RBD):
  • Characterized by abnormal behaviors during REM sleep (talking, shouting, gesturing, flailing arms, punching, kicking) 4
  • Often precedes motor symptoms by years
  • Present in approximately 70% of MSA patients 4

MSA Subtypes

MSA-P (Parkinsonian Type)

• Predominant parkinsonian features (82% of cases) 1
• MRI findings: Putaminal atrophy, hypointensity on T2-weighted images 5

MSA-C (Cerebellar Type)

• Predominant cerebellar syndrome (18% of cases) 1
• MRI findings: Cerebellar and pontine atrophy, "hot cross bun" sign, middle cerebellar peduncle hyperintensity 5

Disease Progression

• Rapid progression: >40% of patients become markedly disabled or wheelchair-bound within 5 years of motor symptom onset 1
• Median survival: 9.5 years from symptom onset 1
• Recurrent urinary tract infections: Major cause of morbidity and mortality (approximately 25% die of related complications) 2

Diagnostic Considerations

• MRI brain is the optimal imaging modality (3T preferable over 1.5T) 5
• Cardiovascular autonomic testing to document orthostatic hypotension 5
• Urodynamic studies to evaluate bladder dysfunction 5
• DaTscan shows decreased radiotracer uptake in the striatum but cannot differentiate MSA from other parkinsonian syndromes 5

Key Diagnostic Pitfalls

• MSA symptoms may be confused with Parkinson's disease but differ in:
  • Poor/unsustained levodopa response
  • Early autonomic failure
  • More rapid progression
• Urological symptoms may be confused with benign prostatic hyperplasia, potentially leading to unnecessary surgery 2
• Symptoms can fluctuate and evolve over time, requiring ongoing reassessment

Red Flags for MSA

• Early autonomic failure with parkinsonism
• Rapid progression of disability
• Poor response to levodopa or early development of levodopa complications
• REM sleep behavior disorder preceding motor symptoms
• Inspiratory stridor

Understanding these typical symptoms is crucial for early diagnosis and appropriate management of MSA, which significantly impacts morbidity, mortality, and quality of life.