Objective: To describe the use of neuroimaging and fluid biomarkers to improve the diagnostic accuracy of early MSA.

Background: The diagnosis of early MSA is difficult as it presents similarly to Parkinson disease (PD). New MDS MSA diagnostic criteria include a clinically‑probable (CP) category based on clinical features. Specialized MRI and fluid biomarkers have promise in improving the diagnosis of MSA. Increased CSF neurofilament light chain [NfL] has been reported in MSA. We describe 3 CP-MSA patients with divergent biomarker data.

Method: Participants with CP-MSA were enrolled in a natural history study (BioMUSE) and had neurologic exam, MRI with quantitative susceptibility mapping [QSM] to measure iron content, and CSF biomarkers (NfL and aggregating α‑synuclein by protein misfolding cyclic amplification [PMCA] assay [Agg‑α‑syn]) assessed at baseline.

Results: Patient 1: A 53-year-old female presented with a 3-year history of urinary and orthostatic hypotension [OH] symptoms, parkinsonism, and REM behavior disorder (RBD). Clinical exam noted Babinski sign, myoclonic tremor, limb ataxia, ataxic dysarthria and axial dystonia. QSM showed increased basal ganglia iron (putamen and globus pallidus externa (GPe)). CSF NfL was 4001.8 pg/mL. The Agg-α‑syn pattern indicated MSA. Multimodal diagnosis: MSA

Patient 2: A 65-year-old male presented with a 2-year history of unexplained voiding difficulties with post void residual, OH and RBD. Clinical exam noted parkinsonism, resting and myoclonic tremor and ataxic gait. QSM showed no evidence of increased iron in basal ganglia or dentate. CSF NfL was 1297.6 pg/mL. The Agg-α‑syn pattern indicated PD. Multimodal diagnosis: PD

Patient 3: A 53-year-old male presented with a 2-year history of unexplained voiding difficulties, OH, poorly responsive parkinsonism, gait dysfunction, RBD and new onset stridor. Clinical exam noted parkinsonism, ataxia, Babinski sign and ataxic dysarthria. QSM showed increased basal ganglia (GPe, substantia nigra) and dentate iron. CSF NfL was 2869.2 pg/mL. The Agg-α‑syn pattern was indeterminate. Multimodal diagnosis: MSA

Conclusion: The diagnosis of early MSA using clinical criteria only is challenging. No single biomarker can be relied on to assure diagnosis. The divergent clinical and biomarker findings in this case series suggest a multimodal clinical-biomarker approach is needed for accurate diagnosis of early MSA.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-multimodal-approach-for-diagnosis-of-early-multiple-system-atrophy-msa/