Nuclear imaging and autonomic biomarkers distinguish pure autonomic failure and predict phenoconversion to widespread alpha-synucleinopathies

<h3>Introduction</h3> Abnormal DaTSCAN is a potential biomarker of central nervous system involvement in pure autonomic failure (PAF) and can predict phenoconversion to more widespread alpha-synucleinopathies. We aimed to describe whether combining DaTSCAN, MIBG cardiac scintigraphy and autonomic biomarkers can help assess likelihood of phenoconversion. <h3>Methods</h3> As part of our longitudinal program on alpha-synucleinopathies, the Queen Square Autonomic Prodromal Project (QSA-PRODOMAL), a subgroup of consecutive patients with an initial diagnosis of PAF underwent a multimodal autonomic and imaging assessment. <h3>Results</h3> 23 PAF patients with available DaTSCAN and cardiac MIBG were included. Within a median disease duration of 8 (IQR 6-12) years, 6 patients phenoconverted: 2 to Lewy body disorders ([LBD], 1 to Parkinson’s disease and 1 to dementia with Lewy bodies), 1 to multiple system atrophy (MSA), and 2 met the research criteria for possible prodromal MSA. Nuclear imaging was abnormal up to 4 years prior to phenoconversion. Both LBD had abnormal DaTSCAN and cardiac MIBG with low supine plasma noradrenaline levels (&lt;200 pg/ml). MSA had abnormal DaTSCAN, normal cardiac MIBG and normal supine plasma noradrenaline levels (&gt;200 pg/mL). The 2 possible prodromal MSA had preserved cardiac innervation and either normal (cerebellar) or abnormal (parkinsonian) DaTSCAN, depending on their clinical phenotype. <h3>Conclusion</h3> The combination of DaTSCAN, cardiac MIBG and noradrenaline profile identified PAF patients at risk of developing more widespread alpha-synucleinopathies and helped predate their phenoconversion by up to 4 years.