Peripheral immunity changes are associated with neurodegeneration and worse clinical outcome in idiopathic normal pressure hydrocephalus.
cerebrospinal fluid biomarkers
idiopathic normal pressure hydrocephalus
immunity
inflammation
neutrophil-to-lymphocyte ratio
Journal
European journal of neurology
ISSN: 1468-1331
Titre abrégé: Eur J Neurol
Pays: England
ID NLM: 9506311
Informations de publication
Date de publication:
21 Dec 2023
21 Dec 2023
Historique:
revised:
21
11
2023
received:
09
10
2023
accepted:
26
11
2023
medline:
22
12
2023
pubmed:
22
12
2023
entrez:
22
12
2023
Statut:
aheadofprint
Résumé
Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical-pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes. We conducted a single-center retrospective-longitudinal 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-β42 (Aβ42), total tau (t-tau), phosphorylated-181-tau, and Evans index. Depending on 5-year outcome, iNPH patients were grouped into "poor outcome" (PO; mRS ≥ 5) and "favorable outcome" (FO; mRS < 5). Biomarkers were compared and correlated with each other. Receiver operating characteristic analysis was performed. iNPH patients compared to controls had higher neutrophil-to-lymphocyte ratio (NLR; 2.43 ± 1.04 vs. 1.61 ± 0.47, p < 0.001), higher neutrophils (4.22 ± 0.86 1000/mL vs. 3.48 ± 1.34, p = 0.033), and lower lymphocytes (1.45 ± 0.55 1000/mL vs. 2.07 ± 0.86, p = 0.038), with the expected CSF biomarkers signature. In the patients' cohort, NLR was associated directly with t-tau and inversely with Aβ42. NLR directly correlated with Evans index. PO patients compared to those with FO had higher NLR (3.25 ± 1.40 vs. 2.01 ± 0.77, p = 0.035) and higher t-tau (274.76 ± 114.39 pg/mL vs. 150.28 ± 72.62, p = 0.017), with an area under the curve of 0.786 and 0.793, respectively. iNPH patients present a proinflammatory state associated with neurodegeneration and predicting poor clinical outcome. Systemic inflammation represents a factor in the clinical-pathological progression of iNPH, and the NLR emerges as a potential prognostic index.
Sections du résumé
BACKGROUND AND PURPOSE
OBJECTIVE
Idiopathic normal pressure hydrocephalus (iNPH) pathogenesis is multifactorial. Systemic inflammation might have a role in gathering clinical-pathological trajectories. We aimed to shape the peripheral immune profile of iNPH and establish correlations with cerebrospinal fluid (CSF) markers, ventricular enlargement, and clinical outcomes.
METHODS
METHODS
We conducted a single-center retrospective-longitudinal 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-β42 (Aβ42), total tau (t-tau), phosphorylated-181-tau, and Evans index. Depending on 5-year outcome, iNPH patients were grouped into "poor outcome" (PO; mRS ≥ 5) and "favorable outcome" (FO; mRS < 5). Biomarkers were compared and correlated with each other. Receiver operating characteristic analysis was performed.
RESULTS
RESULTS
iNPH patients compared to controls had higher neutrophil-to-lymphocyte ratio (NLR; 2.43 ± 1.04 vs. 1.61 ± 0.47, p < 0.001), higher neutrophils (4.22 ± 0.86 1000/mL vs. 3.48 ± 1.34, p = 0.033), and lower lymphocytes (1.45 ± 0.55 1000/mL vs. 2.07 ± 0.86, p = 0.038), with the expected CSF biomarkers signature. In the patients' cohort, NLR was associated directly with t-tau and inversely with Aβ42. NLR directly correlated with Evans index. PO patients compared to those with FO had higher NLR (3.25 ± 1.40 vs. 2.01 ± 0.77, p = 0.035) and higher t-tau (274.76 ± 114.39 pg/mL vs. 150.28 ± 72.62, p = 0.017), with an area under the curve of 0.786 and 0.793, respectively.
CONCLUSIONS
CONCLUSIONS
iNPH patients present a proinflammatory state associated with neurodegeneration and predicting poor clinical outcome. Systemic inflammation represents a factor in the clinical-pathological progression of iNPH, and the NLR emerges as a potential prognostic index.
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Ministero dell'Istruzione, dell'Università e della Ricerca
ID : PNRR-M4C2-I1.3 Project PE_00000019 "HEAL ITALIA"
Informations de copyright
© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.
Références
Andersson IJ, Rosell M, Kockum K, Lilja-Lund O, Söderström L, Laurellid K. Prevalence of idiopathic normal pressure hydrocephalus: a prospective, population-based study. PLoS One. 2019;14(5):e0217705.
Ghosh S, Lippa C. Diagnosis and Prognosis in Idiopathic Normal Pressure Hydrocephalus. Am J Alzheimers Dis Other Demen. 2014;29:583-589.
Relkin N, Marmarou A, Klinge P, Bergsneider M, McL BP. Diagnosing idiopathic normal-pressure hydrocephalus. Neurosurgery. 2005;57:S24-S216.
Bonney PA, Briggs RG, Wu K, et al. Pathophysiological mechanisms underlying idiopathic normal pressure hydrocephalus: a review of recent insights. Front Aging Neurosci. 2022;14:866313.
Wang Z, Zhang Y, Hu F, Ding J, Wang X. Pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus. CNS Neurosci Ther. 2020;26:1230-1240.
Alkhouri N, Morris-Stiff G, Campbell C, et al. Neutrophil to lymphocyte ratio: a new marker for predicting steatohepatitis and fibrosis in patients with nonalcoholic fatty liver disease. Liver Int. 2012;32:297-302.
Buonacera A, Stancanelli B, Colaci M, Malatino L. Neutrophil to lymphocyte ratio: an emerging marker of the relationships between the immune system and diseases. Int J Mol Sci. 2022;23:3636.
Muñoz-Delgado L, Macías-García D, Periñán MT, et al. Peripheral inflammatory immune response differs among sporadic and familial Parkinson's disease. NPJ Parkinsons Dis. 2023;9:12.
Song M, Graubard BI, Rabkin CS, Engels EA. Neutrophil-to-lymphocyte ratio and mortality in the United States general population. Sci Rep. 2021;11:1-9.
Nakajima M, Yamada S, Miyajima M, et al. Guidelines for management of idiopathic normal pressure hydrocephalus (third edition): endorsed by the Japanese society of normal pressure hydrocephalus. Neurol Med Chir (Tokyo). 2021;61:63-97.
Kubo Y, Kazui H, Yoshida T, et al. Validation of grading scale for evaluating symptoms of idiopathic normal-pressure hydrocephalus. Dement Geriatr Cogn Disord. 2007;25:37-45.
Banks JL, Marotta CA. Outcomes validity and reliability of the modified Rankin scale: implications for stroke clinical trials - a literature review and synthesis. Stroke. 2007;38:1091-1096.
Zhou X, Xia J. Application of Evans index in Normal pressure hydrocephalus patients: a mini review. Front Aging Neurosci. 2021;13:783092.
Du W, Zhao X, Wang Y, et al. The PLAN score can predict poor outcomes of intracerebral hemorrhage. Ann Transl Med. 2020;8:14.
Asuzu D, Nystrom K, Amin H, et al. Modest association between the discharge modified Rankin scale score and symptomatic intracerebral hemorrhage after intravenous thrombolysis. J Stroke Cerebrovasc Dis. 2015;24:548-553.
Schirinzi T, Sancesario GM, Di Lazzaro G, et al. Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus. J Neural Transm. 2018;125:673-679.
Oberlin LE, Erickson KI, Mackey R, et al. Peripheral inflammatory biomarkers predict the deposition and progression of amyloid-β in cognitively unimpaired older adults. Brain Behav Immun. 2021;95:178-189.
Jensen MP, Jacobs BM, Dobson R, et al. Lower lymphocyte count is associated with increased risk of Parkinson's disease. Ann Neurol. 2021;89:803.
Bhat TM, Afari ME, Garcia LA. Neutrophil lymphocyte ratio in peripheral vascular disease: a review. Expert Rev Cardiovasc Ther. 2016;14:871-875.
Jeppsson A, Bjerke M, Hellström P, et al. Shared CSF biomarker profile in idiopathic Normal pressure hydrocephalus and subcortical small vessel disease. Front Neurol. 2022;13:839307.
Hänninen JJ, Nakajima M, Vanninen A, et al. Neuropathological findings in possible normal pressure hydrocephalus: A post-mortem study of 29 cases with lifelines. Free Neuropathol. 2022;3:2.
Tan EK, Chao YX, West A, Chan LL, Poewe W, Jankovic J. Parkinson disease and the immune system - associations, mechanisms and therapeutics. Nat Rev Neurol. 2020;16:303-318.
Hou JH, Ou YN, Xu W, Zhang PF, Tan L, Yu JT. Association of peripheral immunity with cognition, neuroimaging, and Alzheimer's pathology. Alzheimers Res Ther. 2022;14:29.
Schirinzi T, Sancesario GM, Ialongo C, et al. A clinical and biochemical analysis in the differential diagnosis of idiopathic normal pressure hydrocephalus. Front Neurol. 2015;6:134833.
Pyrgelis ES, Boufidou F, Constantinides VC, et al. Cerebrospinal fluid biomarkers in iNPH: a narrative review. Diagnostics. 2022;12:2976.
Taghdiri F, Gumus M, Algarni M, Fasano A, Tang-Wai D, Tartaglia MC. Association between cerebrospinal fluid biomarkers and age-related brain changes in patients with normal pressure hydrocephalus. Sci Rep. 2020;10:9106.
Abu-Rumeileh S, Giannini G, Polischi B, et al. Revisiting the cerebrospinal fluid biomarker profile in idiopathic Normal pressure hydrocephalus: the Bologna pro-hydro study. J Alzheimers Dis. 2019;68:723-733.
Braun M, Bjurnemark C, Seo W, et al. Higher levels of neurofilament light chain and total tau in CSF are associated with negative outcome after shunt surgery in patients with normal pressure hydrocephalus. Fluids Barriers CNS. 2022;19:15.
Lukkarinen H, Jeppsson A, Wikkelsö C, et al. Cerebrospinal fluid biomarkers that reflect clinical symptoms in idiopathic normal pressure hydrocephalus patients. Fluids Barriers CNS. 2022;19:11.
Mogensen FLH, Delle C, Nedergaard M. The glymphatic system (En)during inflammation. Int J Mol Sci. 2021;22:7491.
Jaraj D, Wikkelsø C, Rabiei K, et al. Mortality and risk of dementia in normal-pressure hydrocephalus: a population study. Alzheimer's & Dement. 2017;13:850-857.
Andrén K, Wikkelsø C, Sundström N, et al. Survival in treated idiopathic normal pressure hydrocephalus. J Neurol. 2020;267:640-648.
Caimari A, Oliver P, Keijer J, Palou A. Peripheral blood mononuclear cells as a model to study the response of energy homeostasis-related genes to acute changes in feeding conditions. OMICS. 2010;14:129-141.
Shinoda N, Hirai O, Hori S, et al. Utility of MRI-based disproportionately enlarged subarachnoid space hydrocephalus scoring for predicting prognosis after surgery for idiopathic normal pressure hydrocephalus: clinical research. J Neurosurg. 2017;127:1436-1442.
Razay G, Wimmer M, Robertson I. Incidence, diagnostic criteria and outcome following ventriculoperitoneal shunting of idiopathic normal pressure hydrocephalus in a memory clinic population: a prospective observational cross-sectional and cohort study. BMJ Open. 2019;9:e028103.