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We aimed to investigate whether and how Nuclear Magnetic Resonance (NMR)\u2010based metabolomics could differentiate AE from drug\u2010resistant epilepsy (DRE), and stratify AE subtypes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      This study recruited 238 patients: 162 with DRE and 76 AE, including 27 with contactin\u2010associated protein\u2010like 2 (CASPR2), 29 with leucine\u2010rich glioma inactivated 1 (LGI1) and 20 with N\u2010methyl\u2010\n                      <jats:sc>d<\/jats:sc>\n                      \u2010aspartate receptor (NMDAR) antibodies. Plasma samples across the groups were analyzed using NMR spectroscopy and compared with multivariate statistical techniques, such as orthogonal partial least squares discriminant analysis (OPLS\u2010DA).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The OPLS\u2010DA model successfully distinguished AE from DRE patients with a high predictive accuracy of 87.0\u2009\u00b1\u20093.1% (87.9\u2009\u00b1\u20093.4% sensitivity and 86.3\u2009\u00b1\u20093.6% specificity). Further, pairwise OPLS\u2010DA models were able to stratify the three AE subtypes. Plasma metabolomic signatures of AE included decreased high\u2010density lipoprotein (HDL, \u2212(C\n                      <jats:bold>H<\/jats:bold>\n                      <jats:sub>2<\/jats:sub>\n                      )\n                      <jats:sub>n<\/jats:sub>\n                      \u2212, \u2013C\n                      <jats:bold>H<\/jats:bold>\n                      <jats:sub>3<\/jats:sub>\n                      ), phosphatidylcholine and albumin (lysyl moiety). AE subtype\u2010specific metabolomic signatures were also observed, with increased lactate in CASPR2, increased lactate, glucose, and decreased unsaturated fatty acids (UFA, \u2013C\n                      <jats:bold>H<\/jats:bold>\n                      <jats:sub>2<\/jats:sub>\n                      CH=) in LGI1, and increased glycoprotein A (GlycA) in NMDAR\u2010antibody patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This study presents the first non\u2010antibody\u2010based biomarker for differentiating DRE, AE and AE subtypes. These metabolomics signatures underscore the potential relevance of lipid metabolism and glucose regulation in these neurological disorders, offering a promising adjunct to facilitate the diagnosis and therapeutics.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/acn3.52112","type":"journal-article","created":{"date-parts":[[2024,6,22]],"date-time":"2024-06-22T01:20:08Z","timestamp":1719019208000},"page":"1897-1908","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Distinct plasma metabolomic signatures differentiate autoimmune encephalitis from drug\u2010resistant epilepsy"],"prefix":"10.1002","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5713-7305","authenticated-orcid":false,"given":"Wenzheng","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Chemistry University of Oxford  Oxford UK"},{"name":"Department of Pharmacology, Medical Sciences Division University of 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