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The pathophysiology is unknown, but improvement of diagnosis and management requires discovery of novel biomarkers. Our objective was to identify such candidate biomarkers in IIH, and secondarily, test for associations between identified metabolites and disease severity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is a prospective case\u2013control study with collection of cerebrospinal fluid (CSF), serum, and clinical data from new\u2010onset, treatment\u2010na\u00efve patients with IIH (n\u2009=\u200960). Patients were included consecutively from 2 tertiary headache centers in Denmark, and age, sex, and body mass index (BMI) \u2010matched healthy controls (n\u2009=\u200935) were recruited. Clinical data were retrieved at ocular remission (n\u2009=\u200955). Samples were analyzed using non\u2010targeted mass spectrometry.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Serum sphingosine 1\u2010phosphate (S1P), adenosine, and glutamate were 0.46\u2010fold (q\u2009&lt;\u20090.0001), 0.25\u2010fold (q\u2009=\u20090.0048), and 0.44\u2010fold (q\u2009&lt;\u20090.0001) lower, respectively, in IIH. CSF stearoyl\u2010lysophosphatidylcholine (LysoPC\u201018) and 2\u2010palmitoyl\u2010lysophosphatidylcholine (LysoPC\u201016) were 0.42 (q\u2009=\u20090.0025) and 0.37 (q\u2009&lt;\u20090.001) \u2010fold lower. LysoPC\u201018 was higher in patients with moderate\u2013severe versus mild papilledema (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.022). LysoPC\u201018 correlated positively with retinal nerve fiber layer thickness (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.0012, r\u2009=\u20090.42) and inversely with mean deviation on automated perimetry (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01, r\u2009=\u2009\u22120.35). Higher baseline serum S1P (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.018) and lower CSF LysoPC\u201016 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.003) were associated with optic nerve atrophy at ocular remission. Pathway analysis suggests dysregulated lipid metabolism and redox disturbances in new\u2010onset IIH.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>We identify perturbed metabolism in new\u2010onset IIH. S1P and LysoPC\u201016 demonstrate potential prognostic value due to association with subsequent optic nerve atrophy. This association between specific, differential metabolites and outcome provides substantial evidence for novel biomarkers of clinical significance that should be the focus of further targeted studies. ANN NEUROL 2024;96:595\u2013607<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.27010","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T07:20:14Z","timestamp":1719040814000},"page":"595-607","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Metabolic Dysfunction in New\u2010Onset Idiopathic Intracranial Hypertension: Identification of Novel Biomarkers"],"prefix":"10.1002","volume":"96","author":[{"given":"Johanne Juhl","family":"Korsb\u00e6k","sequence":"first","affiliation":[{"name":"Danish Headache Center, Department of Neurology Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rigmor H\u00f8jland","family":"Jensen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology Rigshospitalet  Glostrup Denmark"},{"name":"Translational Research Centre Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3336-157X","authenticated-orcid":false,"given":"Dagmar","family":"Beier","sequence":"additional","affiliation":[{"name":"Headache Clinic, Department of Neurology Odense University Hospital  Odense Denmark"},{"name":"Department of Clinical Research University of Southern Denmark  Odense Denmark"},{"name":"OPEN, Odense Patient data Explorative Network, Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth Arnberg","family":"Wibroe","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Snorre Malm","family":"Hagen","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laleh Dehghani","family":"Molander","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology Odense University Hospital  Odense Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew Paul","family":"Gillum","sequence":"additional","affiliation":[{"name":"Department of Obesity and Liver Pharmacology Novo Nordisk A\/S  Novo Nordisk Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katrine","family":"Svart","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology Rigshospitalet  Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6703-7762","authenticated-orcid":false,"given":"Thomas Folkmann","family":"Hansen","sequence":"additional","affiliation":[{"name":"Danish Headache Center, Department of Neurology Rigshospitalet  Glostrup Denmark"},{"name":"Translational Research Centre Rigshospitalet  Glostrup Denmark"},{"name":"Novo 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