{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:38:34Z","timestamp":1792791514252,"version":"4.5.0"},"reference-count":35,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003407","name":"Ministero dell\u2019Istruzione, dell\u2019Universit\u00e0 e della Ricerca","doi-asserted-by":"publisher","award":["PNRR\u2014M4C2\u2010I1.3 Project PE_00000019 \u201cHEAL ITALIA\u201d"],"award-info":[{"award-number":["PNRR\u2014M4C2\u2010I1.3 Project PE_00000019 \u201cHEAL ITALIA\u201d"]}],"id":[{"id":"10.13039\/501100003407","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical\u2013pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a single\u2010center retrospective\u2013longitudinal study, including 38 iNPH patients and 38 controls. Baseline iNPH Grading Scale and modified Rankin Scale (mRS) scores were collected with peripheral blood cell count, CSF amyloid\u2010\u03b242 (A\u03b242), total tau (t\u2010tau), phosphorylated\u2010181\u2010tau, and Evans index. Depending on 5\u2010year outcome, iNPH patients were grouped into \u201cpoor outcome\u201d (PO; mRS \u2265\u20095) and \u201cfavorable outcome\u201d (FO; mRS\u2009&lt;\u20095). Biomarkers were compared and correlated with each other. Receiver operating characteristic analysis was performed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>iNPH patients compared to controls had higher neutrophil\u2010to\u2010lymphocyte ratio (NLR; 2.43 \u00b1\u20091.04 vs. 1.61 \u00b1\u20090.47, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), higher neutrophils (4.22 \u00b1\u20090.86 1000\/mL vs. 3.48 \u00b1\u20091.34, <jats:italic>p<\/jats:italic>\u2009=\u20090.033), and lower lymphocytes (1.45 \u00b1\u20090.55 1000\/mL vs. 2.07 \u00b1\u20090.86, <jats:italic>p<\/jats:italic>\u2009=\u20090.038), with the expected CSF biomarkers signature. In the patients' cohort, NLR was associated directly with t\u2010tau and inversely with A\u03b242. NLR directly correlated with Evans index. PO patients compared to those with FO had higher NLR (3.25 \u00b1\u20091.40 vs. 2.01 \u00b1\u20090.77, <jats:italic>p<\/jats:italic>\u2009=\u20090.035) and higher t\u2010tau (274.76 \u00b1\u2009114.39 pg\/mL vs. 150.28 \u00b1\u200972.62, <jats:italic>p<\/jats:italic>\u2009=\u20090.017), with an area under the curve of 0.786 and 0.793, respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>iNPH patients present a proinflammatory state associated with neurodegeneration and predicting poor clinical outcome. Systemic inflammation represents a factor in the clinical\u2013pathological progression of iNPH, and the NLR emerges as a potential prognostic index.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.16179","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T06:05:11Z","timestamp":1703225111000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Peripheral immunity changes are associated with neurodegeneration and worse clinical outcome in idiopathic normal pressure hydrocephalus"],"prefix":"10.1111","volume":"31","author":[{"given":"Jacopo","family":"Bissacco","sequence":"first","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Simonetta","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Davide","family":"Mascioli","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Zenuni","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bovenzi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Piergiorgio","family":"Grillo","sequence":"additional","affiliation":[{"name":"Department of Brain and Behavioral Sciences University of Pavia  Pavia Italy"},{"name":"Marlene and Paolo Fresco Institute for Parkinson's Disease and Movement Disorders  New York New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Di\u00a0Giuliano","sequence":"additional","affiliation":[{"name":"Unit of Neuroradiology, Department of Biomedicine and Prevention Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1806-8922","authenticated-orcid":false,"given":"Alessandro","family":"Stefani","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"},{"name":"Parkinson Unit Tor Vergata University Hospital  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicola Biagio","family":"Mercuri","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2517-6278","authenticated-orcid":false,"given":"Tommaso","family":"Schirinzi","sequence":"additional","affiliation":[{"name":"Unit of Neurology, Department of Systems Medicine Tor Vergata University of Rome  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0217705"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1177\/1533317514523485"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000168185.29659.C5"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2022.866313"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/cns.13526"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1478-3231.2011.02639.x"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23073636"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00457-5"},{"key":"e_1_2_9_10_1","first-page":"1","article-title":"Neutrophil\u2010to\u2010lymphocyte ratio and mortality in the United States general population","volume":"11","author":"Song M","year":"2021","journal-title":"Sci Rep"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.2176\/nmc.st.2020-0292"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1159\/000111149"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000258355.23810.c6"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnagi.2021.783092"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2019.11.88"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jstrokecerebrovasdis.2014.09.034"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00702-018-1842-z"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2021.03.015"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.26034"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1586\/14779072.2016.1165091"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2022.839307"},{"key":"e_1_2_9_22_1","article-title":"Neuropathological findings in possible normal pressure hydrocephalus: A post\u2010mortem study of 29 cases with lifelines","volume":"3","author":"H\u00e4nninen JJ","year":"2022","journal-title":"Free Neuropathol"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-0344-4"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13195-022-00968-y"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2015.00086"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12122976"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-66154-y"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3233\/JAD-181012"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00306-2"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12987-022-00309-z"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22147491"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jalz.2017.01.013"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-019-09598-1"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1089\/omi.2009.0092"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.3171\/2016.9.JNS161080"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2018-028103"}],"container-title":["European Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ene.16179","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,18]],"date-time":"2024-03-18T09:44:50Z","timestamp":1710755090000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ene.16179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":35,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,3]]}},"alternative-id":["10.1111\/ene.16179"],"URL":"https:\/\/doi.org\/10.1111\/ene.16179","archive":["Portico"],"relation":{},"ISSN":["1351-5101","1468-1331"],"issn-type":[{"value":"1351-5101","type":"print"},{"value":"1468-1331","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]},"assertion":[{"value":"2023-10-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-26","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e16179"}}