Valerio Nicolella, Marco Varelli, Stefania Fasano, Rosa Sirica, Carmela Polito, Aniello Saviano, Mariano Fiorenza, Federica Novarella, Davide Ranucci, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Castaldo, Daniela Terracciano, Marcello Moccia
{"title":"年龄源性血浆神经丝轻链切断在多发性硬化中的临床应用。","authors":"Valerio Nicolella, Marco Varelli, Stefania Fasano, Rosa Sirica, Carmela Polito, Aniello Saviano, Mariano Fiorenza, Federica Novarella, Davide Ranucci, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Castaldo, Daniela Terracciano, Marcello Moccia","doi":"10.1007/s00415-025-13223-9","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Clinical use of neurofilament light chain (NfL) requires cut-off values that reflect disease status independently of confounding factors, such as age, hemodilution, and cardiovascular risk factors. We compared the performance of different previously suggested cut-offs in separating MS cases and controls, and in identifying different MS clinical features, across age groups.</p><p><strong>Methods: </strong>In this cross-sectional study, we included people with MS (n = 312) and age-, sex-, and eGFR-matched controls (n = 236). For MS cases, we collected descriptor of disease progression (relapsing or progressive), EDSS, and evidence of disease activity in the previous year (including relapses, active MRI, and EDSS progression) and disease duration. Plasma NfL (pNfL) was evaluated using Lumipulse™ fully automated chemiluminescent enzyme immunoassay. We then classified both MS cases and controls based on pNfL suggested by Simrèn et al. (specific for different age ranges), Vermunt et al. (age-derived percentiles), and Benkert et al. (age- and BMI-derived percentiles).</p><p><strong>Results: </strong>In individuals aged 18-50 years, the three suggested pNfL cut-offs provided high specificity (> 85%) in discriminating MS cases and controls (AUC = 0.73; 95%CI = 0.67, 0.78; p = 0.028). In the MS population, the three suggested pNfL cut-offs provided high sensitivity (> 75%) in discriminating relapsing and progressive cases (AUC = 0.70; 95%CI = 0.63, 0.77; p = 0.034), patients with EDSS ≥ 4.0 and EDSS < 4.0 (AUC = 0.69; 95%CI = 0.63, 0.76; p = 0.032), and patients with EDSS ≥ 6.0 and EDSS < 6.0 (AUC = 0.70; 95%CI = 0.62, 0.78; p = 0.040). The three suggested pNfL cut-offs provided lower accuracy in age groups older than 50 years.</p><p><strong>Conclusions: </strong>Previously validated cut-offs provided similar sensitivity and specificity in separating MS cases and controls and in identifying MS clinical features across different age groups, with the best performance before 50 years.</p>","PeriodicalId":16558,"journal":{"name":"Journal of Neurology","volume":"272 8","pages":"495"},"PeriodicalIF":4.8000,"publicationDate":"2025-07-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Clinical application of age-derived cut-offs for plasma neurofilament light chain in multiple sclerosis.\",\"authors\":\"Valerio Nicolella, Marco Varelli, Stefania Fasano, Rosa Sirica, Carmela Polito, Aniello Saviano, Mariano Fiorenza, Federica Novarella, Davide Ranucci, Antonio Carotenuto, Maria Petracca, Roberta Lanzillo, Vincenzo Brescia Morra, Giuseppe Castaldo, Daniela Terracciano, Marcello Moccia\",\"doi\":\"10.1007/s00415-025-13223-9\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Clinical use of neurofilament light chain (NfL) requires cut-off values that reflect disease status independently of confounding factors, such as age, hemodilution, and cardiovascular risk factors. We compared the performance of different previously suggested cut-offs in separating MS cases and controls, and in identifying different MS clinical features, across age groups.</p><p><strong>Methods: </strong>In this cross-sectional study, we included people with MS (n = 312) and age-, sex-, and eGFR-matched controls (n = 236). For MS cases, we collected descriptor of disease progression (relapsing or progressive), EDSS, and evidence of disease activity in the previous year (including relapses, active MRI, and EDSS progression) and disease duration. Plasma NfL (pNfL) was evaluated using Lumipulse™ fully automated chemiluminescent enzyme immunoassay. We then classified both MS cases and controls based on pNfL suggested by Simrèn et al. (specific for different age ranges), Vermunt et al. (age-derived percentiles), and Benkert et al. (age- and BMI-derived percentiles).</p><p><strong>Results: </strong>In individuals aged 18-50 years, the three suggested pNfL cut-offs provided high specificity (> 85%) in discriminating MS cases and controls (AUC = 0.73; 95%CI = 0.67, 0.78; p = 0.028). In the MS population, the three suggested pNfL cut-offs provided high sensitivity (> 75%) in discriminating relapsing and progressive cases (AUC = 0.70; 95%CI = 0.63, 0.77; p = 0.034), patients with EDSS ≥ 4.0 and EDSS < 4.0 (AUC = 0.69; 95%CI = 0.63, 0.76; p = 0.032), and patients with EDSS ≥ 6.0 and EDSS < 6.0 (AUC = 0.70; 95%CI = 0.62, 0.78; p = 0.040). The three suggested pNfL cut-offs provided lower accuracy in age groups older than 50 years.</p><p><strong>Conclusions: </strong>Previously validated cut-offs provided similar sensitivity and specificity in separating MS cases and controls and in identifying MS clinical features across different age groups, with the best performance before 50 years.</p>\",\"PeriodicalId\":16558,\"journal\":{\"name\":\"Journal of Neurology\",\"volume\":\"272 8\",\"pages\":\"495\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-07-09\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Neurology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s00415-025-13223-9\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CLINICAL NEUROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Neurology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s00415-025-13223-9","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CLINICAL NEUROLOGY","Score":null,"Total":0}
Clinical application of age-derived cut-offs for plasma neurofilament light chain in multiple sclerosis.
Objective: Clinical use of neurofilament light chain (NfL) requires cut-off values that reflect disease status independently of confounding factors, such as age, hemodilution, and cardiovascular risk factors. We compared the performance of different previously suggested cut-offs in separating MS cases and controls, and in identifying different MS clinical features, across age groups.
Methods: In this cross-sectional study, we included people with MS (n = 312) and age-, sex-, and eGFR-matched controls (n = 236). For MS cases, we collected descriptor of disease progression (relapsing or progressive), EDSS, and evidence of disease activity in the previous year (including relapses, active MRI, and EDSS progression) and disease duration. Plasma NfL (pNfL) was evaluated using Lumipulse™ fully automated chemiluminescent enzyme immunoassay. We then classified both MS cases and controls based on pNfL suggested by Simrèn et al. (specific for different age ranges), Vermunt et al. (age-derived percentiles), and Benkert et al. (age- and BMI-derived percentiles).
Results: In individuals aged 18-50 years, the three suggested pNfL cut-offs provided high specificity (> 85%) in discriminating MS cases and controls (AUC = 0.73; 95%CI = 0.67, 0.78; p = 0.028). In the MS population, the three suggested pNfL cut-offs provided high sensitivity (> 75%) in discriminating relapsing and progressive cases (AUC = 0.70; 95%CI = 0.63, 0.77; p = 0.034), patients with EDSS ≥ 4.0 and EDSS < 4.0 (AUC = 0.69; 95%CI = 0.63, 0.76; p = 0.032), and patients with EDSS ≥ 6.0 and EDSS < 6.0 (AUC = 0.70; 95%CI = 0.62, 0.78; p = 0.040). The three suggested pNfL cut-offs provided lower accuracy in age groups older than 50 years.
Conclusions: Previously validated cut-offs provided similar sensitivity and specificity in separating MS cases and controls and in identifying MS clinical features across different age groups, with the best performance before 50 years.
期刊介绍：
The Journal of Neurology is an international peer-reviewed journal which provides a source for publishing original communications and reviews on clinical neurology covering the whole field.
In addition, Letters to the Editors serve as a forum for clinical cases and the exchange of ideas which highlight important new findings. A section on Neurological progress serves to summarise the major findings in certain fields of neurology. Commentaries on new developments in clinical neuroscience, which may be commissioned or submitted, are published as editorials.
Every neurologist interested in the current diagnosis and treatment of neurological disorders needs access to the information contained in this valuable journal.
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