What is Shy-Drager Syndrome, also known as Multiple System Atrophy (MSA)?

Shy-Drager Syndrome (Multiple System Atrophy)

Shy-Drager Syndrome, now known as Multiple System Atrophy (MSA), is a rare, progressive, and fatal neurodegenerative disorder characterized by autonomic failure, parkinsonism, cerebellar ataxia, and pyramidal signs in various combinations. 1, 2

Clinical Characteristics

MSA typically presents with:

• Autonomic dysfunction (the hallmark feature):

  • Orthostatic hypotension
  • Urinary incontinence and retention
  • Sexual dysfunction (erectile impotence in males)
  • Gastrointestinal motility issues (constipation)
  • Nocturnal stridor
  • Cardiac arrhythmias 1, 3

• Motor symptoms:

  • Parkinsonism (rigidity and bradykinesia, typically with poor levodopa response)
  • Cerebellar ataxia
  • Pyramidal signs 4, 5

MSA is classified into two main subtypes:

1. MSA-P: Predominant parkinsonism features
2. MSA-C: Predominant cerebellar features 1

Pathophysiology

• MSA is an α-synucleinopathy, characterized by abnormal aggregation of alpha-synuclein protein in glial cells 5
• It involves widespread pathological changes in multiple areas of the central and autonomic nervous systems 3
• The disease typically affects adults in their 50s and 60s, affecting men and women equally 6

Diagnostic Approach

Brain MRI is the preferred initial imaging modality, showing:

• Putaminal atrophy (reduced putamen/caudate volume ratio <1.6)
• Brainstem atrophy (particularly in the pons)
• Cerebellar atrophy
• "Hot cross bun" sign (specific to MSA-C variant) 1

Additional diagnostic tests may include:

• DAT scan to confirm parkinsonism (though it cannot differentiate between MSA and Parkinson's disease)
• Multimodal MRI combining structural, iron-sensitive, and diffusion tensor imaging 1

Features that help differentiate MSA from Parkinson's disease include:

• Marked orthostatic hypotension
• Early urinary symptoms
• Poor response to levodopa
• Cerebellar signs
• Rapid disease progression 4

Management

Management is primarily symptomatic as there are no disease-modifying treatments available:

• For parkinsonism: Levodopa/carbidopa trials, though response is typically poor and may worsen orthostatic hypotension 6, 5
• For autonomic dysfunction:
  • Orthostatic hypotension management (compression stockings, increased salt intake, fludrocortisone)
  • Urinary dysfunction management (intermittent catheterization, anticholinergics)
  • Constipation management (increased fiber, laxatives) 5

Multidisciplinary Care

A coordinated multidisciplinary approach is essential, involving:

• Neurologist (preferably with movement disorder expertise)
• Physical therapist
• Occupational therapist
• Speech therapist
• Urologist
• Pulmonologist
• Palliative care specialist 1

Prognosis

• MSA is progressive and ultimately fatal
• Median survival is approximately 6-10 years from symptom onset
• Early integration of palliative care is recommended, focusing on quality of life and symptom management 1, 2

Important Considerations

• MSA was previously known by various names including Shy-Drager Syndrome, olivopontocerebellar atrophy (OPCA), and striatonigral degeneration 2
• Patients are often misdiagnosed with Parkinson's disease for years due to overlapping symptoms 2
• MSA patients typically show high sensitivity to antiparkinsonian medications, which may worsen orthostatic hypotension 6
• Regular neurological assessments are necessary to monitor disease progression 1

MSA remains a challenging condition with significant unmet needs for patients, highlighting the importance of continued research and advocacy efforts 2.