{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T16:05:20Z","timestamp":1781712320594,"version":"3.54.5"},"reference-count":39,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T00:00:00Z","timestamp":1760918400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006775","name":"GE Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006775","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006775","name":"GE Healthcare","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006775","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Ventricular enlargement is a common finding on brain MRI in patients with gait impairment, particularly in those with idiopathic normal pressure hydrocephalus (iNPH). However, iNPH shares several clinical and radiological features with neurodegenerative diseases, which complicates accurate diagnosis. This study aimed to explore the associations between peripheral immune markers, imaging biomarkers, and final diagnosis in patients with gait disturbance and ventriculomegaly.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively analyzed 55 patients with gait impairment and ventriculomegaly, and 40 age-comparable healthy controls. Clinical assessments included the iNPH Grading Scale (iNPHGS) and cognitive tests. The neutrophil-to-lymphocyte ratio (NLR) was calculated as a peripheral immune marker. Imaging biomarkers included Evans\u2019 index (EI), callosal angle (CA), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) score. Additional cerebrospinal fluid biomarkers and [<jats:sup>18<\/jats:sup>F]-fluorodopa PET\/CT were used when clinically indicated. Patients were classified into two groups at the 5-year follow-up based on current clinical diagnostic criteria, integrating longitudinal clinical evaluation and ancillary investigations. The first group consisted of 35 patients (64%) with a neurodegenerative disorder (ND group), of whom 24 (69%) met criteria for progressive supranuclear palsy, 8 (23%) for Alzheimer\u2019s disease, 2 (6%) for Lewy body dementia, and 1 (3%) for Parkinson\u2019s disease. The remaining 20 patients (36%) fulfilled criteria for probable iNPH and were classified into the iNPH group.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>ND patients had significantly higher NLR (<jats:italic>M<\/jats:italic>\u202f=\u202f2.4, SD\u202f=\u202f0.5) than iNPH patients (<jats:italic>M<\/jats:italic>\u202f=\u202f1.9, SD\u202f=\u202f0.4) and controls (<jats:italic>M<\/jats:italic>\u202f=\u202f1.6, SD\u202f=\u202f0.2; <jats:italic>p<\/jats:italic>\u202f&amp;lt;\u202f0.001). NLR distinguished ND from iNPH with an AUC of 0.79 (80% sensitivity, 70% specificity at a cutoff of 2.0). CA demonstrated strong discrimination (95% sensitivity, 86% specificity). Compared to iNPH, ND had higher iNPHGS scores, greater DESH, and lower CA. Baseline NLR correlated with iNPHGS in ND patients (rs\u202f=\u202f0.48, <jats:italic>p<\/jats:italic>\u202f=\u202f0.004) but not in iNPH. NLR predicted tap test response differently; higher NLR was linked to non-response in ND, and lower NLR associated with improvement in iNPH.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>NLR may serve as a promising peripheral biomarker to differentiate ND from iNPH in patients with gait impairment and ventriculomegaly. Integrating immune, clinical, and imaging markers could improve diagnostic accuracy and guide appropriate therapeutic strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fnagi.2025.1685288","type":"journal-article","created":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:23:38Z","timestamp":1760937818000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Peripheral immunity patterns, imaging features, and clinical outcomes in patients with gait impairment and ventriculomegaly on brain MRI"],"prefix":"10.3389","volume":"17","author":[{"given":"Christian","family":"Espinoza-Vinces","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iciar","family":"Aviles-Olmos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge M.","family":"N\u00fa\u00f1ez-C\u00f3rdoba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Jim\u00e9nez-V\u00e1zquez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Calvo-Imirizaldu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genoveva","family":"Montoya-Murillo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Mart\u00ed-Andr\u00e9s","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Arbizu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda-Rosario","family":"Luquin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,20]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"e0217705","DOI":"10.1371\/journal.pone.0217705","article-title":"Prevalence of idiopathic normal pressure hydrocephalus: a prospective, population-based study","volume":"14","author":"Andersson","year":"2019","journal-title":"PLoS One"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1097\/PSY.0000000000000620","article-title":"The role of norepinephrine and \u03b1-adrenergic receptors in acute stress-induced changes in granulocytes and monocytes","volume":"80","author":"Beis","year":"2018","journal-title":"Psychosom. Med."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"e16179","DOI":"10.1111\/ene.16179","article-title":"Peripheral immunity changes are associated with neurodegeneration and worse clinical outcome in idiopathic normal pressure hydrocephalus","volume":"31","author":"Bissacco","year":"2023","journal-title":"Eur. J. Neurol. [Epub ahead of print]"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1033","DOI":"10.3233\/JAD-150107","article-title":"A simplified callosal angle measure best differentiates idiopathic-normal pressure hydrocephalus from neurodegenerative dementia","volume":"46","author":"Cagnin","year":"2015","journal-title":"J Alzheimer's Dis"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1002\/ana.25046","article-title":"Deconstructing normal pressure hydrocephalus: ventriculomegaly as early sign of neurodegeneration","volume":"82","author":"Espay","year":"2017","journal-title":"Ann. Neurol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"351","DOI":"10.2214\/ajr.149.2.35","article-title":"MR signal abnormalities at 1.5 T in Alzheimer\u2019s dementia and normal aging","volume":"149","author":"Fazekas","year":"1987","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1002\/brb3.2884","article-title":"Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: an imaging reminder of atypical parkinsonism","volume":"13","author":"Fu","year":"2023","journal-title":"Brain Behav."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"583","DOI":"10.1177\/1533317514523485","article-title":"Diagnosis and prognosis in idiopathic normal pressure hydrocephalus","volume":"29","author":"Ghosh","year":"2014","journal-title":"Am. J. Alzheimers Dis. Other Dement."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"853","DOI":"10.1002\/mds.26987","article-title":"Clinical diagnosis of progressive supranuclear palsy: the movement disorder society criteria","volume":"32","author":"H\u00f6glinger","year":"2017","journal-title":"Mov. Disord."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.1111\/ene.14235","article-title":"The neutrophil-to-lymphocyte ratio as a marker of peripheral inflammation in progressive supranuclear palsy: a retrospective study","volume":"27","author":"Inci","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.jalz.2018.02.018","article-title":"NIA-AA research framework: toward a biological definition of Alzheimer\u2019s disease","volume":"14","author":"Jack","year":"2018","journal-title":"Alzheimers Dement."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"108295","DOI":"10.1016\/j.clineuro.2024.108295","article-title":"Idiopathic normal pressure hydrocephalus: validation of the desh score as a prognostic tool for shunt surgery response","volume":"241","author":"J\u00f3hannsd\u00f3ttir","year":"2024","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"e200431","DOI":"10.1212\/CPJ.0000000000200431","article-title":"Disproportionately enlarged subarachnoid-space hydrocephalus on MRI in pathologically confirmed progressive supranuclear palsy","volume":"15","author":"Kawazoe","year":"2025","journal-title":"Continuum (Minneap. Minn.)"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1007\/s00401-020-02158-2","article-title":"Distribution patterns of tau pathology in progressive supranuclear palsy","volume":"140","author":"Kovacs","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1159\/000111149","article-title":"Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus","volume":"25","author":"Kubo","year":"2008","journal-title":"Dement. Geriatr. Cogn. Disord."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41598-023-48940-6","article-title":"Relationship between disproportionately enlarged subarachnoid-space hydrocephalus and white matter tract integrity in normal pressure hydrocephalus","volume":"15","author":"Lee","year":"2023","journal-title":"Front. Aging Neurosci."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"1009","DOI":"10.1007\/s00415-012-6745-6","article-title":"Normal pressure hydrocephalus or progressive supranuclear palsy? A clinicopathological case series","volume":"260","author":"Magdalinou","year":"2013","journal-title":"J. Neurol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1212\/WNL.0000000000004058","article-title":"Diagnosis and management of dementia with Lewy bodies: fourth consensus report of the DLB consortium","volume":"89","author":"McKeith","year":"2017","journal-title":"Neurology"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e0305322","DOI":"10.1371\/journal.pone.0305322","article-title":"Neutrophil to lymphocyte ratio in Alzheimer's disease: a systematic review and meta-analysis","volume":"19","author":"Mohammadi","year":"2024","journal-title":"PLoS One"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"5201","DOI":"10.1007\/s10072-022-06119-3","article-title":"Parkinsonism in idiopathic normal pressure hydrocephalus: is it time for defining a clinical tetrad?","volume":"43","author":"Mostile","year":"2022","journal-title":"Neurol. Sci."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1038\/s41531-023-00457-5","article-title":"Peripheral inflammatory immune response differs among sporadic and familial Parkinson\u2019s disease","volume":"9","author":"Mu\u00f1oz-Delgado","year":"2023","journal-title":"NPJ Parkinsons Dis."},{"key":"ref001","doi-asserted-by":"publisher","first-page":"e16451","DOI":"10.1111\/ene.1645","article-title":"Peripheral immune profile and neutrophil-to-lymphocyte ratio in progressive supranuclear palsy: case-control study and meta-analysis","volume":"31","author":"Mu\u00f1oz-Delgado","year":"2024","journal-title":"Eur. J. Neurol."},{"key":"ref22","doi-asserted-by":"publisher","first-page":"63","DOI":"10.2176\/nmc.st.2020-0292","article-title":"Guidelines for management of idiopathic normal pressure hydrocephalus (third edition): endorsed by the Japanese Society of Normal Pressure Hydrocephalus","volume":"61","author":"Nakajima","year":"2021","journal-title":"Neurol. Med. Chir. (Tokyo)"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"346","DOI":"10.1111\/jnc.15561","article-title":"Dopaminergic imaging in degenerative parkinsonisms, an established clinical diagnostic tool","volume":"164","author":"Nicastro","year":"2023","journal-title":"J. Neurochem."},{"key":"ref24","doi-asserted-by":"publisher","first-page":"1930","DOI":"10.1111\/ene.14322","article-title":"Progressive supranuclear palsy often develops idiopathic normal pressure hydrocephalus-like magnetic resonance imaging features","volume":"27","author":"Ohara","year":"2020","journal-title":"Eur. J. Neurol."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"803","DOI":"10.1038\/sj.jcbfm.9600389","article-title":"In vivo presynaptic and postsynaptic striatal dopamine functions in idiopathic normal pressure hydrocephalus","volume":"27","author":"Ouchi","year":"2007","journal-title":"J. Cereb. Blood Flow Metab."},{"key":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1212\/WNL.0000000000213352","article-title":"Involvement of the nigrostriatal pathway in patients with idiopathic normal pressure hydrocephalus and parkinsonism","volume":"213352","author":"Palermo","year":"2025","journal-title":"Neurology"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"105290","DOI":"10.1016\/j.parkreldis.2023.105290","article-title":"Longitudinal clinical decline and baseline predictors in progressive supranuclear palsy","volume":"107","author":"Pavone","year":"2023","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref28","doi-asserted-by":"publisher","first-page":"123250","DOI":"10.1016\/j.jns.2024.123250","article-title":"Diagnostic importance of disproportionately enlarged subarachnoid space hydrocephalus and callosal angle measurements in the context of normal pressure hydrocephalus: a useful tool for clinicians","volume":"466","author":"Petersen","year":"2024","journal-title":"J. Neurol. Sci."},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.1002\/mds.26424","article-title":"MDS clinical diagnostic criteria for Parkinson\u2019s disease","volume":"30","author":"Postuma","year":"2015","journal-title":"Mov. Disord."},{"key":"ref30","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1002\/mds.28366","article-title":"Striatal dopamine deficit and motor impairment in idiopathic normal pressure hydrocephalus","volume":"36","author":"Pozzi","year":"2021","journal-title":"Mov. Disord."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"2097","DOI":"10.1007\/s00234-022-03051-3","article-title":"Commentary: predictor of shunt response in idiopathic normal pressure hydrocephalus","volume":"64","author":"Rovira","year":"2022","journal-title":"Neuroradiology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1186\/s12987-021-00298-5","article-title":"The timed up and go test in idiopathic normal pressure hydrocephalus: a nationwide study of 1300 patients","volume":"19","author":"Sundstr\u00f6m","year":"2022","journal-title":"Fluids Barriers CNS."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1111\/j.1532-5415.1992.tb01992.x","article-title":"The mini-mental state examination: a comprehensive review","volume":"40","author":"Tombaugh","year":"1992","journal-title":"J. Am. Geriatr. Soc."},{"key":"ref34","doi-asserted-by":"publisher","first-page":"107308","DOI":"10.1016\/j.parkreldis.2025.107308","article-title":"Post-shunt prognosis in patients with idiopathic normal-pressure hydrocephalus and comorbid progressive supranuclear palsy: a retrospective, single-center study in Japan","volume":"135","author":"Uchigami","year":"2025","journal-title":"Parkinsonism Relat. Disord."},{"key":"ref35","doi-asserted-by":"publisher","first-page":"100780","DOI":"10.1016\/j.cophys.2024.100780","article-title":"Adrenergic modulation of neutrophil and macrophage functions: pathophysiological cues","volume":"41","author":"Vida","year":"2024","journal-title":"Curr. Opin. Physio."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1230","DOI":"10.1111\/cns.13526","article-title":"Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus","volume":"26","author":"Wang","year":"2020","journal-title":"CNS Neurosci. Ther."},{"key":"ref37","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1111\/j.1600-0404.1986.tb04601.x","article-title":"Normal pressure hydrocephalus. Predictive value of the cerebrospinal fluid tap-test","volume":"73","author":"Wikkels\u00f6","year":"1986","journal-title":"Acta Neurol. Scand."},{"key":"ref38","first-page":"5","article-title":"Ratio of neutrophil to lymphocyte counts--rapid and simple parameter of systemic inflammation and stress in critically ill","volume":"102","author":"Zahorec","year":"2001","journal-title":"Bratisl. Lek. Listy"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1685288\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,20]],"date-time":"2025-10-20T05:23:39Z","timestamp":1760937819000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2025.1685288\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,20]]},"references-count":39,"alternative-id":["10.3389\/fnagi.2025.1685288"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2025.1685288","relation":{},"ISSN":["1663-4365"],"issn-type":[{"value":"1663-4365","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,20]]},"article-number":"1685288"}}