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Auton. Res."],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      The autonomic synucleinopathy multiple system atrophy (MSA) can be difficult to distinguish clinically from Parkinson disease with orthostatic hypotension (PD+OH).\n                      <jats:sup>18<\/jats:sup>\n                      F-Dopamine positron emission tomography separates these conditions based on cardiac noradrenergic deficiency in PD+OH and not in MSA but is available only at the NIH Clinical Center. 3,4-Dihydroxyphenylglycol (DHPG) is the main neuronal metabolite of norepinephrine. This retrospective observational study examined whether DHPG levels in cerebrospinal fluid (CSF) or plasma differentiate MSA from PD+OH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We reviewed CSF and plasma neurochemical data from all patients referred for evaluation at the NIH Clinical Center between 1995 and 2024 for chronic autonomic failure or parkinsonism. A concurrently studied comparison group included healthy volunteers or patients with orthostatic intolerance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      CSF DHPG was decreased in MSA (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200967,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001) compared to the controls but also tended to be decreased in PD+OH (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200931,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0776). Antecubital venous plasma DHPG was decreased in PD+OH (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200947,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0064) but not in MSA. CSF\/plasma concentration ratios of DHPG were lower in MSA than in PD+OH (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0005). Cardiac arteriovenous increments in plasma DHPG and cardiac norepinephrine spillovers were strikingly decreased in PD+OH (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u20096) and were lower than in MSA (\n                      <jats:italic>N<\/jats:italic>\n                      \u2009=\u200920,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001 each). Combining cardiac arteriovenous increments in plasma DHPG with norepinephrine spillovers completely separated PD+OH from MSA.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>CSF\/plasma ratios of DHPG, cardiac arteriovenous increments in plasma DHPG, and cardiac norepinephrine spillovers separate MSA from PD+OH. On the basis of our results we propose that biomarker combinations involving DHPG in biofluids may enable a clinical laboratory distinction of MSA from PD+OH.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s10286-025-01150-8","type":"journal-article","created":{"date-parts":[[2025,9,17]],"date-time":"2025-09-17T18:31:09Z","timestamp":1758133869000},"page":"807-815","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["3,4-Dihydroxyphenylglycol levels separate multiple system atrophy from Parkinson disease with orthostatic hypotension"],"prefix":"10.1007","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5709-9940","authenticated-orcid":false,"given":"David S.","family":"Goldstein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patti","family":"Sullivan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney","family":"Holmes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,9,17]]},"reference":[{"key":"1150_CR1","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/S0304-3940(98)00407-8","volume":"249","author":"K Wakabayashi","year":"1998","unstructured":"Wakabayashi K, Yoshimoto M, Tsuji S, Takahashi H (1998) Alpha-synuclein immunoreactivity in glial cytoplasmic inclusions in multiple system atrophy. 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