Can a diagnosis of multiple system atrophy (MSA) be made in a patient with parkinsonism, autonomic dysfunction, and cerebellar ataxia, with a negative Dopamine Transporter (DaT) scan?

Can MSA Be Diagnosed with a Negative DaTscan?

No, a diagnosis of multiple system atrophy (MSA) cannot be made in the context of a truly negative DaTscan, as a normal dopamine transporter scan essentially excludes all parkinsonian syndromes, including MSA. 1

Why a Negative DaTscan Rules Out MSA

DaTscan Findings in Parkinsonian Syndromes

• A normal I-123 ioflupane SPECT/CT (DaTscan) essentially excludes parkinsonian syndromes, including MSA, Parkinson's disease, progressive supranuclear palsy, and corticobasal degeneration. 1

• MSA is a synucleinopathy characterized by α-synuclein accumulation in glial cytoplasmic inclusions, which causes dopaminergic neuronal loss in the striatum. 2, 3

• Ioflupane SPECT/CT demonstrates abnormal dopaminergic depletion patterns in MSA, showing decreased radiotracer uptake in the striatum, though it cannot distinguish MSA from other parkinsonian syndromes like PD, PSP, or CBD. 3

Clinical Implications

The presence of parkinsonism is a core feature of MSA, occurring in 87% of cases with bradykinesia and rigidity. 2, 3 Since parkinsonian syndromes require dopaminergic neuronal loss to manifest clinically, and DaTscan directly measures presynaptic dopamine transporter density, a negative scan indicates intact dopaminergic neurons and therefore excludes the diagnosis. 1

Reconsidering the Clinical Picture

Alternative Diagnoses to Consider

If a patient presents with symptoms suggestive of MSA but has a normal DaTscan, you must reconsider the diagnosis entirely:

• Autoimmune cerebellitis or cerebellar degeneration - Consider if cerebellar ataxia is prominent, with testing for coeliac antibodies, anti-GQ1b, and vitamin E levels. 4

• Spinocerebellar ataxias (SCA) - Genetic testing should be pursued if there is cerebellar predominance without true parkinsonism. 4

• Pure autonomic failure - This can present with isolated autonomic dysfunction without motor features and would not show DaTscan abnormalities. 5, 6

• Functional neurological disorder - Particularly if symptoms are inconsistent or atypical for neurodegenerative disease. 1

Critical Pitfall to Avoid

Do not assume the DaTscan is falsely negative. The sensitivity of DaTscan for detecting parkinsonian syndromes is extremely high, and false negatives are exceptionally rare in the context of true dopaminergic neurodegeneration. 1 If the clinical picture strongly suggests parkinsonism but the DaTscan is normal, the patient either:

1. Does not have a parkinsonian syndrome
2. Has drug-induced parkinsonism (which would show normal DaTscan)
3. Has a functional movement disorder mimicking parkinsonism

Diagnostic Criteria for MSA

Consensus Diagnostic Requirements

According to established consensus criteria, MSA diagnosis requires specific combinations of clinical features:

• Probable MSA requires autonomic failure/urinary dysfunction PLUS poorly levodopa-responsive parkinsonism OR cerebellar ataxia. 5, 6

• Possible MSA requires one criterion plus two features from separate domains (autonomic, parkinsonian, cerebellar, or corticospinal). 5, 6

• Definite MSA requires pathological confirmation. 5, 6

The 2022 International Parkinson and Movement Disorder Society Criteria

The most recent criteria enable diagnosis of clinically established MSA, clinically probable MSA, prodromal possible MSA, and definite pathologic MSA. 7 However, all of these categories presume the presence of a neurodegenerative parkinsonian syndrome, which would be excluded by a normal DaTscan. 1

Recommended Diagnostic Approach

When Clinical Suspicion Remains High

If you strongly suspect MSA based on clinical features but encounter a normal DaTscan:

1. Obtain MRI brain without contrast as the optimal structural imaging modality to look for characteristic patterns of regional atrophy (putaminal rim sign, hot cross bun sign, cerebellar atrophy). 3

2. Reassess the clinical examination for true bradykinesia and rigidity versus other movement abnormalities that may mimic parkinsonism. 1

3. Document autonomic testing including tilt-table testing, urodynamic studies, and cardiovascular autonomic function tests to objectively confirm autonomic failure. 8

4. Consider repeat DaTscan in 6-12 months if symptoms progress and clinical suspicion remains high, as very early disease might theoretically not yet show abnormalities (though this would be exceptionally rare). 1

5. Pursue alternative diagnoses as outlined above, particularly autoimmune and genetic causes of ataxia with autonomic dysfunction. 4

Specialist Referral

General neurologists or movement disorder specialists should confirm any suspected parkinsonian syndrome diagnosis because correctly diagnosing these conditions on clinical features alone is challenging. 1 This is especially critical when imaging results conflict with clinical impressions.