What is the workup for Shy-Drager syndrome?

Workup for Shy-Drager Syndrome (Multiple System Atrophy with Autonomic Predominance)

Brain MRI is the first-line imaging test for suspected Shy-Drager syndrome, followed by autonomic function testing including orthostatic blood pressure measurements and Ioflupane SPECT/CT to differentiate from other parkinsonian disorders. 1

Clinical Presentation Assessment

Key Clinical Features to Identify

• Autonomic dysfunction (primary feature):

  • Orthostatic hypotension (blood pressure drop ≥20/10 mmHg within 3 minutes of standing)
  • Urinary incontinence and bladder dysfunction
  • Erectile dysfunction in males
  • Constipation and fecal incontinence
  • Anhidrosis (decreased sweating)

• Parkinsonian features:

  • Rigidity and bradykinesia (typically without prominent tremor)
  • Poor response to levodopa therapy
  • Postural instability with early falls

• Other neurological signs:

  • Cerebellar ataxia
  • Pyramidal signs
  • Nocturnal stridor
  • REM sleep behavior disorder

Diagnostic Algorithm

Step 1: Initial Testing

• Complete blood count to rule out anemia
• Basic metabolic panel to assess renal function and electrolytes
• Thyroid function tests
• Vitamin B12 and folate levels
• Orthostatic vital sign measurements (supine and standing blood pressure/heart rate)
• Electrocardiogram to assess for cardiac arrhythmias

Step 2: Neuroimaging

• Brain MRI - First-line imaging modality 1
  • Look for characteristic findings:
    • Putaminal atrophy with hypointensity
    • "Hot cross bun" sign in pons
    • Cerebellar atrophy
    • Atrophy of middle cerebellar peduncles

Step 3: Autonomic Function Testing

• Tilt-table testing with continuous blood pressure monitoring
• Plasma and urinary catecholamine measurements (typically at lower limit of normal and fail to increase during orthostasis) 2
• Cardiovascular autonomic testing (heart rate response to deep breathing, Valsalva maneuver)
• Sudomotor function testing (quantitative sudomotor axon reflex test)

Step 4: Urological Assessment

• Post-void residual measurement
• Urodynamic studies to document neurogenic bladder

Step 5: Nuclear Medicine Imaging

• Ioflupane (I-123) SPECT/CT (DaTscan) 1
  • Helps differentiate MSA from essential tremor
  • Shows abnormal patterns of dopaminergic depletion
  • Note: Cannot differentiate MSA from Parkinson's disease alone

Step 6: Sleep Studies

• Polysomnography to assess for REM sleep behavior disorder
  • Look for increased electromyographic activity during REM sleep (lack of atonia) 1

Differential Diagnosis Considerations

• Parkinson's disease

  • Key differentiators: MSA shows more prominent early autonomic failure, poor levodopa response, and faster progression

• Pure autonomic failure

  • Key differentiator: Lacks parkinsonian or cerebellar features

• Progressive supranuclear palsy

  • Key differentiator: Vertical gaze palsy, different pattern on MRI

• Lewy body dementia

  • Key differentiator: Early cognitive impairment, visual hallucinations

Common Pitfalls to Avoid

1. Misdiagnosing as Parkinson's disease - The poor response to levodopa therapy and prominent early autonomic symptoms should raise suspicion for MSA 3

2. Overlooking drug-induced orthostatic hypotension - Always review medications that can cause orthostatic hypotension (antihypertensives, antidepressants, antipsychotics)

3. Missing secondary causes of autonomic dysfunction - Diabetes, amyloidosis, and autoimmune neuropathies can mimic some features

4. Excessive levodopa treatment - Can worsen orthostatic hypotension in MSA patients 4

5. Failing to recognize REM sleep behavior disorder - Often precedes motor symptoms by years and is highly predictive of synucleinopathies

By following this systematic approach, clinicians can effectively diagnose Shy-Drager syndrome (now classified as a subtype of Multiple System Atrophy with predominant autonomic features) and distinguish it from other parkinsonian disorders.