Multiple System Atrophy Diagnostic Criteria
Multiple System Atrophy (MSA) is diagnosed based on the presence of autonomic failure plus either parkinsonism or cerebellar ataxia, with specific clinical and imaging features that distinguish it from other neurodegenerative disorders.
Clinical Diagnostic Categories
Definite MSA
- Requires pathological confirmation showing alpha-synuclein positive glial cytoplasmic inclusions with neurodegenerative changes in striatonigral or olivopontocerebellar structures 1
Probable MSA
- Requires the criterion for autonomic failure/urinary dysfunction plus poorly levodopa-responsive parkinsonism or cerebellar ataxia 1
- Autonomic failure manifests as orthostatic hypotension (systolic drop ≥20 mmHg or diastolic drop ≥10 mmHg) and/or urinary incontinence/incomplete bladder emptying
Possible MSA
- Requires one criterion plus two features from separate other domains 1
- Domains include autonomic dysfunction, parkinsonism, cerebellar ataxia, and corticospinal dysfunction
Clinical Subtypes
MSA-P (Parkinsonian Variant)
- Predominant extrapyramidal/parkinsonian features
- Accounts for approximately 80% of MSA cases 2
- Key features:
- Akinesia and rigidity
- Poor or unsustained response to levodopa
- Postural instability
- Asymmetric presentation in 74% of cases 3
MSA-C (Cerebellar Variant)
- Predominant cerebellar ataxia
- Accounts for approximately 20% of MSA cases 2
- Key features:
- Gait ataxia
- Limb ataxia
- Cerebellar dysarthria
- Oculomotor dysfunction
MSA-A (Autonomic Variant)
- Less commonly recognized subtype where autonomic dysfunction predominates 2
- Previously known as Shy-Drager syndrome
Key Diagnostic Features
Autonomic Dysfunction (required for probable MSA)
- Orthostatic hypotension (drop in systolic BP ≥20 mmHg or diastolic BP ≥10 mmHg within 3 minutes of standing)
- Urinary symptoms: incontinence, retention, incomplete emptying
- Sexual dysfunction (erectile dysfunction in males is often an early symptom)
- Constipation and gastrointestinal dysfunction
- Anhidrosis (reduced sweating)
Motor Features
Parkinsonism:
Cerebellar signs:
- Gait and limb ataxia
- Cerebellar dysarthria
- Nystagmus
- Dysmetria
Additional Features
- Pyramidal signs (present in 61% of cases) 3
- Rapid disease progression (>40% of patients markedly disabled within 5 years) 3
- Median survival of approximately 9.5 years from symptom onset 3
Imaging Features
- MRI brain without contrast is the optimal imaging modality 2
- Key findings:
- MSA-P: Putaminal atrophy with T2 hyperintensity
- MSA-C: Cerebellar and pontine atrophy ("hot cross bun" sign)
- Progressive marked degeneration of the neostriatum
Diagnostic Pitfalls and Challenges
Temporal Evolution
- Autonomic symptoms are the initial feature in 41% of patients but eventually develop in 97% 3
- Median interval between onset of motor and autonomic symptoms is approximately 2 years (range up to 14 years) 4
- Early diagnosis is difficult when patients present with isolated autonomic failure or isolated motor symptoms 4
Differential Diagnosis
- Parkinson's disease
- Progressive supranuclear palsy
- Corticobasal degeneration
- Cerebellar ataxias
- Pure autonomic failure
- Lewy body dementia
- Vascular parkinsonism
- Multifocal cerebral ischemia 2
Atypical Features
- Dementia (not typical but can occur)
- Hallucinations (more suggestive of Lewy body dementia)
- Vertical gaze palsy (more suggestive of progressive supranuclear palsy) 4
Management Considerations
- No disease-modifying therapy currently exists 5
- Treatment focuses on symptomatic management of autonomic dysfunction and motor symptoms 5, 6
- Multidisciplinary care involving neurologists, autonomic specialists, and primary care providers is essential 5
Early diagnosis of MSA remains challenging due to overlapping features with other neurodegenerative disorders. The combination of progressive autonomic failure with poorly levodopa-responsive parkinsonism or cerebellar ataxia remains the cornerstone of clinical diagnosis, with definitive diagnosis requiring pathological confirmation.