Natural history of Pure autonomic failure – the Queen square experience

<h3>Objective</h3> To describe the natural history of pure autonomic failure (PAF) in a longitudinal cohort of patients. <h3>Methods</h3> As part of the Queen Square Autonomic Prodromal Project (QSA-PRODROMAL), 271 patients with an initial diagnosis of PAF were followed for up to 37 years from symptoms’ onset (T0). Clinical features were assessed yearly. Autonomic function testing (AFT) was performed at first assessment (T1) in all patients, and after a mean follow-up (T2) of 6±4 years in a subgroup of 145 patients. <h3>Results</h3> Mean age at onset was 60±11 years. Mean disease duration (T0 to last follow-up, T3) was 13±8 years. At T3, 74% patients retained a PAF phenotype, while 14% and 9% converted to LBD or MSA, respectively. 43% patients died during follow-up (59% PAF, 25% LBD, 14% MSA). Widespread cardiovascular autonomic failure was present in all patients on both AFTs. Severe neurogenic orthostatic hypotension (nOH) was present in 45% patients at T1 and T2. Supine hypertension was present in up to 97% at T2. 55% patients were on vasopressor medications at T1, and 67% at T2. <h3>Conclusion</h3> Patients with PAF presented with severe and progressive autonomic failure. A third of patients converted to widespread alpha-synucleinopathies after a long prodromal phase of up to 31 years. NOH is severe and refractory to treatment in almost 50% of patients, and it might represent a risk factor for disease progression and mortality.