Objective: To report cases in which combined α-synuclein PET and body fluid α-synuclein seeds amplification assay (SAA) enabled biological diagnosis of multiple system atrophy–cerebellar type (MSA-C) prior to fulfillment of clinical diagnostic criteria.

Background: MSA is a progressive neurodegenerative disorder in which substantial neuronal loss is often present at diagnosis. Early diagnosis of MSA-C is particularly challenging before overt autonomic dysfunction develops. Recent advances in α-synuclein biomarkers, including PET and SAA, may enable diagnosis at preclinical or very early stages.

Method: Two patients clinically suspected of MSA-C who were positive for both an α-synuclein fibril–targeting PET radioligand (¹⁸F-SPAL-T-06) and blood α-synuclein SAA were included. Both underwent clinical evaluation, DAT-SPECT, cerebral perfusion SPECT, MRI, and [¹¹C]PiB PET.

Results: Case 1 was a 59-year-old man with REM sleep behavior disorder. DAT-SPECT showed a mild reduction in striatal binding, while perfusion SPECT revealed marked cerebellar hypoperfusion. He had gait instability without overt autonomic dysfunction. [¹¹C]PiB PET was negative. [¹⁸F]SPAL-T-06 PET demonstrated increased uptake in the bilateral middle cerebellar peduncles and cerebellar white matter with cerebellar predominance. Blood SAA was positive.

Case 2 was a 53-year-old woman with impaired fine motor control, frequent falls, and dysarthria approximately 6 months after symptom onset. MRI showed the hot cross bun sign and middle cerebellar peduncle atrophy. Perfusion SPECT revealed cerebellar hypoperfusion, and DAT-SPECT showed a mild change. [¹¹C]PiB PET was negative. [¹⁸F]SPAL-T-06 PET demonstrated similar cerebellar-predominant uptake. Blood SAA was positive.

In both cases, the biological findings strongly suggested MSA-C in the absence of overt autonomic dysfunction.

Conclusion: Combined α-synuclein PET and SAA may enable the biological diagnosis of MSA-C at a relatively early stage before clinical criteria are met. Early identification may be critical for disease-modifying interventions. Larger longitudinal studies are needed to validate biomarker-based early diagnosis and its clinical impact.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/ultra-early-diagnosis-of-msa-c-using-biological-biomarkers-a-two-case-study-employing-%ce%b1-synuclein-pet-and-fluid-%ce%b1-synuclein-seeds-amplification-assay-saa/