{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T15:17:12Z","timestamp":1784042232233,"version":"3.55.0"},"reference-count":43,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2025,7,22]],"date-time":"2025-07-22T00:00:00Z","timestamp":1753142400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100015873","name":"National Brain Appeal","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100015873","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000627","name":"Guarantors of Brain","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000627","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ann Clin Transl Neurol"],"published-print":{"date-parts":[[2025,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Pure autonomic failure (PAF) presents with autonomic failure without other neurological features. A third develop central neurological features, fulfilling criteria for multiple system atrophy (MSA) and Lewy body diseases (LBD), including Parkinson's disease and Dementia with Lewy bodies. We hypothesized multimodal autonomic biomarkers would identify differences between PAF, MSA, and LBD, and predict phenoconversion in patients presenting with PAF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This observational cohort study included 391 alpha\u2010synucleinopathy patients evaluated with cardiovascular autonomic testing, plasma noradrenaline, pupillometry, autonomic symptom, and quality\u2010of\u2010life questionnaires. PAF patients were monitored for the emergence of central neurological features. Logistic regression modeling was used to identify autonomic biomarkers at initial assessment that predicted future phenoconversion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Patients with PAF had more severe orthostatic hypotension, lower supine plasma noradrenaline, and frequent sympathetic pupillary deficits at initial assessment than MSA and LBD. 50\/194 (26%) with PAF phenoconverted to MSA or LBD after a median of 13\u2009years, with normal pupils, heart rate response to deep breathing \u2265\u200910\u2009bpm, and supine plasma noradrenaline \u2265\u2009200\u2009pg\/mL predicting future phenoconversion to MSA or LBD, with younger age at presentation and higher supine plasma noradrenaline levels associated with conversion to MSA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In patients presenting with PAF, normal pupillary function and supine plasma noradrenaline levels with intact cardiovagal responses were red flags for future phenoconversion. Younger patients with higher supine plasma noradrenaline levels were more likely to convert to MSA rather than LBD. A non\u2010invasive multimodal autonomic assessment can help differentiate between alpha\u2010synucleinopathies and predict phenoconversion from PAF to MSA or LBD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.70140","type":"journal-article","created":{"date-parts":[[2025,7,23]],"date-time":"2025-07-23T06:49:49Z","timestamp":1753253389000},"page":"2170-2180","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Multimodal Autonomic Biomarkers Predict Phenoconversion in Pure Autonomic Failure"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0860-9211","authenticated-orcid":false,"given":"S.","family":"Koay","sequence":"first","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"},{"name":"Department of Translational Neuroscience and Stroke University College London Queen Square Institute of Neurology  London UK"},{"name":"Queen Square Centre for Neuromuscular Diseases National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6183-0997","authenticated-orcid":false,"given":"E.","family":"Vichayanrat","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Bremner","sequence":"additional","affiliation":[{"name":"Department of Translational Neuroscience and Stroke University College London Queen Square Institute of Neurology  London UK"},{"name":"Neuro\u2010Ophthalmology Department National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F.","family":"Valerio","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Mackenzie","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Chiaro","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Ingle","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P.","family":"McNamara","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Watson","sequence":"additional","affiliation":[{"name":"Autonomic Unit National Hospital for Neurology and Neurosurgery  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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