{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T15:48:41Z","timestamp":1791388121380,"version":"4.3.3"},"reference-count":64,"publisher":"Springer Science and Business Media LLC","issue":"7","license":[{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T00:00:00Z","timestamp":1714348800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Medizinische Hochschule Hannover (MHH)"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Neurol"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Objective<\/jats:title>\n                <jats:p>To evaluate the performance of serum neurofilament light chain (NfL) and cerebrospinal fluid (CSF) phosphorylated neurofilament heavy chain (pNfH) as diagnostic biomarkers for the differentiation between motor neuron disease (MND) and multifocal motor neuropathy (MMN).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>This retrospective, monocentric study included 16 patients with MMN and 34 incident patients with MND. A subgroup of lower motor neuron (MN) dominant MND patients (<jats:italic>n<\/jats:italic>\u2009=\u200924) was analyzed separately. Serum NfL was measured using Ella automated immunoassay, and CSF pNfH was measured using enzyme-linked immunosorbent assay. Area under the curve (AUC), optimal cutoff values (Youden\u2019s index), and correlations with demographic characteristics were calculated.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Neurofilament concentrations were significantly higher in MND compared to MMN (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and serum NfL and CSF pNfH correlated strongly with each other (Spearman\u2019s rho 0.68, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Serum NfL (AUC 0.946, sensitivity and specificity 94%) and CSF pNfH (AUC 0.937, sensitivity 90.0%, specificity 100%) performed excellent in differentiating MND from MMN. Optimal cutoff values were\u2009\u2265\u200944.15\u00a0pg\/mL (serum NfL) and\u2009\u2265\u2009715.5\u00a0pg\/mL (CSF pNfH), respectively. Similar results were found when restricting the MND cohort to lower MN dominant patients. Only one MMN patient had serum NfL above the cutoff. Two MND patients presented with neurofilament concentrations below the cutoffs, both featuring a slowly progressive disease.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>Neurofilaments are valuable supportive biomarkers for the differentiation between MND and MMN. Serum NfL and CSF pNfH perform similarly well and elevated neurofilaments in case of diagnostic uncertainty underpin MND diagnosis.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00415-024-12355-8","type":"journal-article","created":{"date-parts":[[2024,4,29]],"date-time":"2024-04-29T13:02:06Z","timestamp":1714395726000},"page":"4441-4452","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Diagnostic value of neurofilaments in differentiating motor neuron disease from multifocal motor neuropathy"],"prefix":"10.1007","volume":"271","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3035-4638","authenticated-orcid":false,"given":"Camilla","family":"Wohnrade","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tabea","family":"Seeliger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Gingele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bogdan","family":"Bjelica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Skripuletz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Petri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,4,29]]},"reference":[{"issue":"5","key":"12355_CR1","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","volume":"21","author":"SA Goutman","year":"2022","unstructured":"Goutman SA, Hardiman O, Al-Chalabi A et al (2022) Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis. Lancet Neurol 21(5):480\u2013493. https:\/\/doi.org\/10.1016\/S1474-4422(21)00465-8","journal-title":"Lancet Neurol"},{"issue":"2","key":"12355_CR2","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1056\/NEJMra1603471","volume":"377","author":"RH Brown","year":"2017","unstructured":"Brown RH, Al-Chalabi A (2017) Amyotrophic lateral sclerosis. N Engl J Med 377(2):162\u2013172. https:\/\/doi.org\/10.1056\/NEJMra1603471","journal-title":"N Engl J Med"},{"key":"12355_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2020.117054","volume":"417","author":"D Richards","year":"2020","unstructured":"Richards D, Morren JA, Pioro EP (2020) Time to diagnosis and factors affecting diagnostic delay in amyotrophic lateral sclerosis. J Neurol Sci 417:117054. https:\/\/doi.org\/10.1016\/j.jns.2020.117054","journal-title":"J Neurol Sci"},{"issue":"3","key":"12355_CR4","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.clinph.2007.09.143","volume":"119","author":"M de Carvalho","year":"2008","unstructured":"de Carvalho M, Dengler R, Eisen A et al (2008) Electrodiagnostic criteria for diagnosis of ALS. Clin Neurophysiol 119(3):497\u2013503. https:\/\/doi.org\/10.1016\/j.clinph.2007.09.143","journal-title":"Clin Neurophysiol"},{"issue":"5","key":"12355_CR5","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1080\/146608200300079536","volume":"1","author":"BR Brooks","year":"2000","unstructured":"Brooks BR, Miller RG, Swash M et al (2000) El escorial revisited: revised criteria for the diagnosis of amyotrophic lateral sclerosis. Amyotroph Lateral Scler 1(5):293\u2013299. https:\/\/doi.org\/10.1080\/146608200300079536","journal-title":"Amyotroph Lateral Scler"},{"issue":"8","key":"12355_CR6","doi-asserted-by":"publisher","first-page":"1975","DOI":"10.1016\/j.clinph.2020.04.005","volume":"131","author":"JM Shefner","year":"2020","unstructured":"Shefner JM, Al-Chalabi A, Baker MR et al (2020) A proposal for new diagnostic criteria for ALS. Clin Neurophysiol 131(8):1975\u20131978. https:\/\/doi.org\/10.1016\/j.clinph.2020.04.005","journal-title":"Clin Neurophysiol"},{"issue":"5","key":"12355_CR7","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1002\/mus.27392","volume":"64","author":"S Vucic","year":"2021","unstructured":"Vucic S, Ferguson TA, Cummings C et al (2021) Gold Coast diagnostic criteria: implications for ALS diagnosis and clinical trial enrollment. Muscle Nerve 64(5):532\u2013537. https:\/\/doi.org\/10.1002\/mus.27392","journal-title":"Muscle Nerve"},{"issue":"10","key":"12355_CR8","doi-asserted-by":"publisher","first-page":"1928","DOI":"10.1016\/j.clinph.2013.03.025","volume":"124","author":"A Uncini","year":"2013","unstructured":"Uncini A, Susuki K, Yuki N (2013) Nodo-paranodopathy: beyond the demyelinating and axonal classification in anti-ganglioside antibody-mediated neuropathies. Clin Neurophysiol 124(10):1928\u20131934. https:\/\/doi.org\/10.1016\/j.clinph.2013.03.025","journal-title":"Clin Neurophysiol"},{"issue":"5","key":"12355_CR9","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1097\/WCO.0000000000000605","volume":"31","author":"K Beadon","year":"2018","unstructured":"Beadon K, Guimar\u00e3es-Costa R, L\u00e9ger J (2018) Multifocal motor neuropathy. Curr Opin Neurol 31(5):559\u2013564. https:\/\/doi.org\/10.1097\/WCO.0000000000000605","journal-title":"Curr Opin Neurol"},{"issue":"3","key":"12355_CR10","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/jns.12583","volume":"28","author":"M Di Egidio","year":"2023","unstructured":"Di Egidio M, Bacaglio CR, Arrejor\u00eda R et al (2023) Evidence for spontaneous regulation of the humoral IgM anti-GM1 autoimmune response by IgG antibodies in multifocal motor neuropathy patients. J Peripher Nerv Syst 28(3):398\u2013406. https:\/\/doi.org\/10.1111\/jns.12583","journal-title":"J Peripher Nerv Syst"},{"issue":"4","key":"12355_CR11","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0125339","volume":"10","author":"K Kollewe","year":"2015","unstructured":"Kollewe K, Wurster U, Sinzenich T et al (2015) Anti-ganglioside antibodies in amyotrophic lateral sclerosis revisited. PLoS ONE 10(4):e0125339. https:\/\/doi.org\/10.1371\/journal.pone.0125339","journal-title":"PLoS ONE"},{"key":"12355_CR12","volume-title":"Multifocal motor neuropathy","author":"S Hameed","year":"2023","unstructured":"Hameed S, Cascella M (2023) Multifocal motor neuropathy. StatPearls Publishing, Treasure Island"},{"issue":"4","key":"12355_CR13","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1002\/mus.27922","volume":"68","author":"J Tavee","year":"2023","unstructured":"Tavee J, Brannagan Thomas H, Lenihan MW et al (2023) Updated consensus statement: Intravenous immunoglobulin in the treatment of neuromuscular disorders report of the AANEM ad hoc committee. Muscle Nerve 68(4):356\u201374. https:\/\/doi.org\/10.1002\/mus.27922","journal-title":"Muscle Nerve"},{"key":"12355_CR14","doi-asserted-by":"publisher","unstructured":"European Federation of Neurological Societies\/Peripheral Nerve Society Guideline on management of multifocal motor neuropathy. Report of a Joint Task Force of the European Federation of Neurological Societies and the Peripheral Nerve Society\u2014first revision. (2010) J Peripher Nerv Syst. 15(4):295\u2013301. https:\/\/doi.org\/10.1111\/j.1529-8027.2010.00290.x.","DOI":"10.1111\/j.1529-8027.2010.00290.x"},{"issue":"14","key":"12355_CR15","doi-asserted-by":"publisher","first-page":"e1610","DOI":"10.1212\/WNL.0000000000007242","volume":"92","author":"L van den Berg","year":"2019","unstructured":"van den Berg L, Sorenson E, Gronseth G et al (2019) Revised airlie house consensus guidelines for design and implementation of ALS clinical trials. Neurology 92(14):e1610\u2013e1623. https:\/\/doi.org\/10.1212\/WNL.0000000000007242","journal-title":"Neurology"},{"issue":"1","key":"12355_CR16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1146\/annurev.ne.19.030196.001155","volume":"19","author":"MK Lee","year":"1996","unstructured":"Lee MK, Cleveland DW (1996) Neuronal intermediate filaments. Annu Rev Neurosci 19(1):187\u2013217. https:\/\/doi.org\/10.1146\/annurev.ne.19.030196.001155","journal-title":"Annu Rev Neurosci"},{"key":"12355_CR17","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2021.679199","volume":"15","author":"F Verde","year":"2021","unstructured":"Verde F, Otto M, Silani V (2021) Neurofilament light chain as biomarker for amyotrophic lateral sclerosis and frontotemporal dementia. Front Neurosci 15:679199. https:\/\/doi.org\/10.3389\/fnins.2021.679199","journal-title":"Front Neurosci"},{"issue":"8","key":"12355_CR18","doi-asserted-by":"publisher","first-page":"870","DOI":"10.1136\/jnnp-2018-320106","volume":"90","author":"L Gaetani","year":"2019","unstructured":"Gaetani L, Blennow K, Calabresi P et al (2019) Neurofilament light chain as a biomarker in neurological disorders. J Neurol Neurosurg Psychiatr. 90(8):870. https:\/\/doi.org\/10.1136\/jnnp-2018-320106","journal-title":"J Neurol Neurosurg Psychiatr."},{"issue":"2","key":"12355_CR19","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1016\/j.neuron.2016.07.007","volume":"91","author":"M Bacioglu","year":"2016","unstructured":"Bacioglu M, Maia LF, Preische O et al (2016) Neurofilament light chain in blood and CSF as marker of disease progression in mouse models and in neurodegenerative diseases. Neuron. 91(2):494\u20136. https:\/\/doi.org\/10.1016\/j.neuron.2016.07.007","journal-title":"Neuron."},{"key":"12355_CR20","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2018.01167","author":"K Poesen","year":"2019","unstructured":"Poesen K, Van Damme P (2019) Diagnostic and prognostic performance of neurofilaments in ALS. Front Neurol. https:\/\/doi.org\/10.3389\/fneur.2018.01167","journal-title":"Front Neurol"},{"key":"12355_CR21","doi-asserted-by":"publisher","DOI":"10.3390\/life13061301","author":"G Mccluskey","year":"2023","unstructured":"Mccluskey G, Morrison KE, Donaghy C et al (2023) Serum neurofilaments in motor neuron disease and their utility in differentiating ALS, PMA and PLS. Life. https:\/\/doi.org\/10.3390\/life13061301","journal-title":"Life"},{"issue":"3","key":"12355_CR22","doi-asserted-by":"publisher","first-page":"163","DOI":"10.1093\/braincomms\/fcad163","volume":"5","author":"JC Davies","year":"2023","unstructured":"Davies JC, Dharmadasa T, Thompson AG et al (2023) Limited value of serum neurofilament light chain in diagnosing amyotrophic lateral sclerosis. Brain Commun 5(3):163. https:\/\/doi.org\/10.1093\/braincomms\/fcad163","journal-title":"Brain Commun"},{"issue":"9","key":"12355_CR23","doi-asserted-by":"publisher","first-page":"2810","DOI":"10.1111\/ene.15428","volume":"29","author":"I Kmezic","year":"2022","unstructured":"Kmezic I, Samuelsson K, Finn A et al (2022) Neurofilament light chain and total tau in the differential diagnosis and prognostic evaluation of acute and chronic inflammatory polyneuropathies. Euro J of Neurol. 29(9):2810. https:\/\/doi.org\/10.1111\/ene.15428","journal-title":"Euro J of Neurol."},{"issue":"6","key":"12355_CR24","doi-asserted-by":"publisher","first-page":"1699","DOI":"10.1007\/s00415-020-09761-z","volume":"267","author":"S Abu-Rumeileh","year":"2020","unstructured":"Abu-Rumeileh S, Vacchiano V, Zenesini C et al (2020) Diagnostic-prognostic value and electrophysiological correlates of CSF biomarkers of neurodegeneration and neuroinflammation in amyotrophic lateral sclerosis. J Neurol 267(6):1699\u20131708. https:\/\/doi.org\/10.1007\/s00415-020-09761-z","journal-title":"J Neurol"},{"issue":"4","key":"12355_CR25","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1136\/jnnp-2019-322541","volume":"91","author":"MR Turner","year":"2020","unstructured":"Turner MR, Barohn RJ, Corcia P et al (2020) Primary lateral sclerosis: consensus diagnostic criteria. J Neurol Neurosurg Psychiatr 91(4):373\u2013377. https:\/\/doi.org\/10.1136\/jnnp-2019-322541","journal-title":"J Neurol Neurosurg Psychiatr"},{"issue":"1","key":"12355_CR26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s41073-016-0014-7","volume":"1","author":"DA Korevaar","year":"2015","unstructured":"Korevaar DA, Cohen JF, Reitsma JB et al (2015) Updating standards for reporting diagnostic accuracy: the development of STARD 2015. Res Integr Peer Rev 1(1):7. https:\/\/doi.org\/10.1186\/s41073-016-0014-7","journal-title":"Res Integr Peer Rev"},{"issue":"11","key":"12355_CR27","doi-asserted-by":"publisher","first-page":"1103","DOI":"10.1002\/mus.880141111","volume":"14","author":"RP Kleyweg","year":"1991","unstructured":"Kleyweg RP, Der Mech\u00e9 V, Frans GA, Schmitz PIM (1991) Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barr\u00e9 syndrome. Muscle Nerve 14(11):1103\u20131109. https:\/\/doi.org\/10.1002\/mus.880141111","journal-title":"Muscle Nerve"},{"issue":"1","key":"12355_CR28","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1016\/s0022-510x(99)00210-5","volume":"169","author":"JM Cedarbaum","year":"1999","unstructured":"Cedarbaum JM, Stambler N, Malta E et al (1999) The ALSFRS-R: a revised ALS functional rating scale that incorporates assessments of respiratory function. J Neurol Sci 169(1):13\u201321. https:\/\/doi.org\/10.1016\/s0022-510x(99)00210-5","journal-title":"J Neurol Sci"},{"issue":"2","key":"12355_CR29","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1212\/01.wnl.0000194316.91908.8a","volume":"66","author":"F Kimura","year":"2006","unstructured":"Kimura F, Fujimura C, Ishida S et al (2006) Progression rate of ALSFRS-R at time of diagnosis predicts survival time in ALS. Neurology 66(2):265\u2013267. https:\/\/doi.org\/10.1212\/01.wnl.0000194316.91908.8a","journal-title":"Neurology"},{"key":"12355_CR30","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-021-01499-6","author":"A Behzadi","year":"2021","unstructured":"Behzadi A, Pujol-Calder\u00f3n F, Tjust AE et al (2021) Neurofilaments can differentiate ALS subgroups and ALS from common diagnostic mimics. Sci Rep. https:\/\/doi.org\/10.1038\/s41598-021-01499-6","journal-title":"Sci Rep"},{"issue":"4","key":"12355_CR31","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1136\/jnnp-2017-316605","volume":"89","author":"M De Schaepdryver","year":"2018","unstructured":"De Schaepdryver M, Jeromin A, Gille B et al (2018) Comparison of elevated phosphorylated neurofilament heavy chains in serum and cerebrospinal fluid of patients with amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 89(4):367\u2013373. https:\/\/doi.org\/10.1136\/jnnp-2017-316605","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"12355_CR32","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1136\/jnnp-2015-311387","volume":"87","author":"P Steinacker","year":"2016","unstructured":"Steinacker P, Feneberg E, Weishaupt J et al (2016) Neurofilaments in the diagnosis of motoneuron diseases: a prospective study on 455 patients. J Neurol Neurosurg Psychiatry 87(1):12\u201320. https:\/\/doi.org\/10.1136\/jnnp-2015-311387","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"12355_CR33","doi-asserted-by":"publisher","first-page":"726","DOI":"10.3389\/fneur.2018.00726","volume":"9","author":"D Li","year":"2018","unstructured":"Li D, Ren H, Jeromin A et al (2018) Diagnostic performance of neurofilaments in chinese patients with amyotrophic lateral sclerosis: a prospective study. Front Neurol 9:726. https:\/\/doi.org\/10.3389\/fneur.2018.00726","journal-title":"Front Neurol"},{"issue":"1\u20132","key":"12355_CR34","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1080\/21678421.2023.2263874","volume":"25","author":"U Kl\u00e4ppe","year":"2023","unstructured":"Kl\u00e4ppe U, Sennf\u00e4lt S, Lovik A et al (2023) Neurodegenerative biomarkers outperform neuroinflammatory biomarkers in amyotrophic lateral sclerosis. Amyotroph Later Scler Frontotemporal Degener 25(1\u20132):150\u2013161. https:\/\/doi.org\/10.1080\/21678421.2023.2263874","journal-title":"Amyotroph Later Scler Frontotemporal Degener"},{"issue":"1","key":"12355_CR35","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1136\/jnnp-2021-327129","volume":"93","author":"S Halbgebauer","year":"2022","unstructured":"Halbgebauer S, Steinacker P, Verde F et al (2022) Comparison of CSF and serum neurofilament light and heavy chain as differential diagnostic biomarkers for ALS. J Neurol Neurosurg Psychiatry 93(1):68\u201374. https:\/\/doi.org\/10.1136\/jnnp-2021-327129","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"1","key":"12355_CR36","doi-asserted-by":"publisher","first-page":"e22","DOI":"10.1212\/WNL.0000000000004761","volume":"90","author":"E Feneberg","year":"2018","unstructured":"Feneberg E, Oeckl P, Steinacker P et al (2018) Multicenter evaluation of neurofilaments in early symptom onset amyotrophic lateral sclerosis. Neurology 90(1):e22-30. https:\/\/doi.org\/10.1212\/WNL.0000000000004761","journal-title":"Neurology"},{"issue":"6","key":"12355_CR37","doi-asserted-by":"publisher","first-page":"1600","DOI":"10.1111\/ene.15773","volume":"30","author":"T Meyer","year":"2023","unstructured":"Meyer T, Salkic E, Grehl TT et al (2023) Performance of serum neurofilament light chain in a wide spectrum of clinical courses of amyotrophic lateral sclerosis\u2014a cross-sectional multicenter study. Euro J of Neurology. 30(6):1600. https:\/\/doi.org\/10.1111\/ene.15773","journal-title":"Euro J of Neurology."},{"issue":"1","key":"12355_CR38","doi-asserted-by":"publisher","first-page":"e59","DOI":"10.1212\/WNL.0000000000009559","volume":"95","author":"M Benatar","year":"2020","unstructured":"Benatar M, Zhang L, Wang L et al (2020) Validation of serum neurofilaments as prognostic and potential pharmacodynamic biomarkers for ALS. Neurology 95(1):e59-69. https:\/\/doi.org\/10.1212\/WNL.0000000000009559","journal-title":"Neurology"},{"key":"12355_CR39","doi-asserted-by":"publisher","first-page":"919","DOI":"10.3389\/fneur.2020.00919","volume":"11","author":"Q Sun","year":"2020","unstructured":"Sun Q, Zhao X, Li S et al (2020) CSF neurofilament light chain elevation predicts ALS severity and progression. Front Neurol 11:919. https:\/\/doi.org\/10.3389\/fneur.2020.00919","journal-title":"Front Neurol"},{"issue":"3","key":"12355_CR40","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1111\/nan.12511","volume":"45","author":"B Gille","year":"2019","unstructured":"Gille B, De Schaepdryver M, Goossens J et al (2019) Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol 45(3):291\u2013304. https:\/\/doi.org\/10.1111\/nan.12511","journal-title":"Neuropathol Appl Neurobiol"},{"issue":"2","key":"12355_CR41","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1136\/jnnp-2018-318704","volume":"90","author":"F Verde","year":"2019","unstructured":"Verde F, Steinacker P, Weishaupt JH et al (2019) Neurofilament light chain in serum for the diagnosis of amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 90(2):157\u2013164. https:\/\/doi.org\/10.1136\/jnnp-2018-318704","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"12355_CR42","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000004029","author":"K Poesen","year":"2017","unstructured":"Poesen K, De Schaepdryver M, Stubendorff B et al (2017) Neurofilament markers for ALS correlate with extent of upper and lower motor neuron disease. Neurology. https:\/\/doi.org\/10.1212\/WNL.0000000000004029","journal-title":"Neurology"},{"issue":"1","key":"12355_CR43","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1186\/s12883-016-0689-x","volume":"16","author":"X Chen","year":"2016","unstructured":"Chen X, Chen Y, Wei Q et al (2016) Assessment of a multiple biomarker panel for diagnosis of amyotrophic lateral sclerosis. BMC Neurol 16(1):173. https:\/\/doi.org\/10.1186\/s12883-016-0689-x","journal-title":"BMC Neurol"},{"issue":"5","key":"12355_CR44","doi-asserted-by":"publisher","first-page":"e2997,n\/a","DOI":"10.1002\/brb3.2997","volume":"13","author":"J Li","year":"2023","unstructured":"Li J, Dai Y, Sun X et al (2023) Comparison of neurofilament light and heavy chain in spinal muscular atrophy and amyotrophic lateral sclerosis: a pilot study. Brain and behavior 13(5):e2997,n\/a. https:\/\/doi.org\/10.1002\/brb3.2997","journal-title":"Brain and behavior"},{"issue":"2","key":"12355_CR45","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1210\/clinem\/dgac580","volume":"108","author":"S Ciardullo","year":"2023","unstructured":"Ciardullo S, Muraca E, Bianconi E et al (2023) Diabetes mellitus is associated with higher serum neurofilament light chain levels in the general US population. J Clin Endocrinol Metab 108(2):361\u2013367. https:\/\/doi.org\/10.1210\/clinem\/dgac580","journal-title":"J Clin Endocrinol Metab"},{"issue":"2","key":"12355_CR46","doi-asserted-by":"publisher","first-page":"fcaa166","DOI":"10.1093\/braincomms\/fcaa166","volume":"2","author":"AA Polymeris","year":"2020","unstructured":"Polymeris AA, Coslovksy M, Aeschbacher S et al (2020) Serum neurofilament light in atrial fibrillation: clinical, neuroimaging and cognitive correlates. Brain Commun 2(2):fcaa166. https:\/\/doi.org\/10.1093\/braincomms\/fcaa166","journal-title":"Brain Commun"},{"issue":"3","key":"12355_CR47","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1111\/jns.12575","volume":"28","author":"V Fridman","year":"2023","unstructured":"Fridman V, Sillau S, Ritchie A et al (2023) Plasma neurofilament light chain concentrations are elevated in youth-onset type 2 diabetes and associated with neuropathy. J Peripher Nerv Syst 28(3):460\u2013470. https:\/\/doi.org\/10.1111\/jns.12575","journal-title":"J Peripher Nerv Syst"},{"issue":"5","key":"12355_CR48","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1001\/jamaneurol.2016.5398","volume":"74","author":"A Gaiani","year":"2017","unstructured":"Gaiani A, Martinelli I, Bello L et al (2017) Diagnostic and prognostic biomarkers in amyotrophic lateral sclerosis: neurofilament light chain levels in definite subtypes of disease. JAMA Neurol 74(5):525\u2013532. https:\/\/doi.org\/10.1001\/jamaneurol.2016.5398","journal-title":"JAMA Neurol"},{"issue":"12","key":"12355_CR49","doi-asserted-by":"publisher","first-page":"1329","DOI":"10.1111\/j.1468-1331.2007.01972.x","volume":"14","author":"H Zetterberg","year":"2007","unstructured":"Zetterberg H, Jacobsson J, Rosengren L et al (2007) Cerebrospinal fluid neurofilament light levels in amyotrophic lateral sclerosis: impact of SOD1 genotype. Eur J Neurol 14(12):1329\u20131333. https:\/\/doi.org\/10.1111\/j.1468-1331.2007.01972.x","journal-title":"Eur J Neurol"},{"issue":"3","key":"12355_CR50","doi-asserted-by":"publisher","first-page":"510","DOI":"10.1007\/s00415-017-8730-6","volume":"265","author":"D Rossi","year":"2018","unstructured":"Rossi D, Volanti P, Brambilla L et al (2018) CSF neurofilament proteins as diagnostic and prognostic biomarkers for amyotrophic lateral sclerosis. J Neurol 265(3):510\u2013521. https:\/\/doi.org\/10.1007\/s00415-017-8730-6","journal-title":"J Neurol"},{"issue":"9","key":"12355_CR51","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0075091","volume":"8","author":"J Gaiottino","year":"2013","unstructured":"Gaiottino J, Norgren N, Dobson R et al (2013) Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS ONE 8(9):e75091. https:\/\/doi.org\/10.1371\/journal.pone.0075091","journal-title":"PLoS ONE"},{"issue":"9","key":"12355_CR52","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1001\/jamaneurol.2019.1534","volume":"76","author":"C Bridel","year":"2019","unstructured":"Bridel C, van Wieringen WN, Zetterberg H et al (2019) Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. Arch Neurol (Chicago) 76(9):1035\u20131048. https:\/\/doi.org\/10.1001\/jamaneurol.2019.1534","journal-title":"Arch Neurol (Chicago)"},{"issue":"2","key":"12355_CR53","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1111\/ene.14063","volume":"27","author":"E Thouvenot","year":"2020","unstructured":"Thouvenot E, Demattei C, Lehmann S et al (2020) Serum neurofilament light chain at time of diagnosis is an independent prognostic factor of survival in amyotrophic lateral sclerosis. Eur J Neurol 27(2):251\u2013257. https:\/\/doi.org\/10.1111\/ene.14063","journal-title":"Eur J Neurol"},{"issue":"12","key":"12355_CR54","doi-asserted-by":"publisher","first-page":"1561","DOI":"10.1111\/j.1468-1331.2012.03777.x","volume":"19","author":"R Tortelli","year":"2012","unstructured":"Tortelli R, Ruggieri M, Cortese R et al (2012) Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression. Eur J Neurol 19(12):1561\u20131567. https:\/\/doi.org\/10.1111\/j.1468-1331.2012.03777.x","journal-title":"Eur J Neurol"},{"issue":"4","key":"12355_CR55","doi-asserted-by":"publisher","first-page":"436","DOI":"10.1136\/jnnp-2019-322309","volume":"91","author":"M De Schaepdryver","year":"2020","unstructured":"De Schaepdryver M, Lunetta C, Tarlarini C et al (2020) Neurofilament light chain and C reactive protein explored as predictors of survival in amyotrophic lateral sclerosis. J Neurol Neurosurg Psychiatry 91(4):436\u2013437. https:\/\/doi.org\/10.1136\/jnnp-2019-322309","journal-title":"J Neurol Neurosurg Psychiatry"},{"issue":"10","key":"12355_CR56","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.1515\/cclm-2015-1195","volume":"54","author":"J Kuhle","year":"2016","unstructured":"Kuhle J, Barro C, Andreasson U et al (2016) Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence immunoassay and Simoa. Clin Chem Lab Med 54(10):1655\u20131661. https:\/\/doi.org\/10.1515\/cclm-2015-1195","journal-title":"Clin Chem Lab Med"},{"issue":"1","key":"12355_CR57","doi-asserted-by":"publisher","first-page":"4041","DOI":"10.1038\/s41598-023-29704-8","volume":"13","author":"M Truffi","year":"2023","unstructured":"Truffi M, Garofalo M, Ricciardi A et al (2023) Neurofilament-light chain quantification by Simoa and Ella in plasma from patients with dementia: a comparative study. Sci Rep 13(1):4041. https:\/\/doi.org\/10.1038\/s41598-023-29704-8","journal-title":"Sci Rep"},{"issue":"3","key":"12355_CR58","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1111\/jns.12279","volume":"23","author":"S Mariotto","year":"2018","unstructured":"Mariotto S, Farinazzo A, Magliozzi R et al (2018) Serum and cerebrospinal neurofilament light chain levels in patients with acquired peripheral neuropathies. J Peripher Nerv Syst 23(3):174\u2013177. https:\/\/doi.org\/10.1111\/jns.12279","journal-title":"J Peripher Nerv Syst"},{"issue":"1\u20132","key":"12355_CR59","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.jim.2013.11.008","volume":"402","author":"MJA Koel-Simmelink","year":"2014","unstructured":"Koel-Simmelink MJA, Vennegoor A, Killestein J et al (2014) The impact of pre-analytical variables on the stability of neurofilament proteins in CSF, determined by a novel validated SinglePlex Luminex assay and ELISA. J Immunol Methods 402(1\u20132):43\u201349. https:\/\/doi.org\/10.1016\/j.jim.2013.11.008","journal-title":"J Immunol Methods"},{"issue":"22","key":"12355_CR60","doi-asserted-by":"publisher","first-page":"2247","DOI":"10.1212\/WNL.0000000000001642","volume":"84","author":"C Lu","year":"2015","unstructured":"Lu C, Macdonald-Wallis C, Gray E et al (2015) Neurofilament light chain: a prognostic biomarker in amyotrophic lateral sclerosis. Neurology 84(22):2247\u20132257. https:\/\/doi.org\/10.1212\/WNL.0000000000001642","journal-title":"Neurology"},{"issue":"1\u20132","key":"12355_CR61","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1080\/21678421.2016.1241279","volume":"18","author":"P Steinacker","year":"2017","unstructured":"Steinacker P, Huss A, Mayer B et al (2017) Diagnostic and prognostic significance of neurofilament light chain NF-L, but not progranulin and S100B, in the course of amyotrophic lateral sclerosis: data from the German MND-net. Amyotroph Lateral scler Frontotemporal Degener 18(1\u20132):112\u2013119. https:\/\/doi.org\/10.1080\/21678421.2016.1241279","journal-title":"Amyotroph Lateral scler Frontotemporal Degener"},{"issue":"1","key":"12355_CR62","doi-asserted-by":"publisher","first-page":"19594","DOI":"10.1038\/s41598-023-46179-9","volume":"13","author":"G Nagel","year":"2023","unstructured":"Nagel G, Kurz D, Peter RS et al (2023) Cystatin C based estimation of chronic kidney disease and amyotrophic lateral sclerosis in the ALS registry Swabia: associated risk and prognostic value. Sci Rep. 13(1):19594. https:\/\/doi.org\/10.1038\/s41598-023-46179-9","journal-title":"Sci Rep."},{"issue":"14","key":"12355_CR63","doi-asserted-by":"publisher","first-page":"11682","DOI":"10.3390\/ijms241411682","volume":"24","author":"N Kittipeerapat","year":"2023","unstructured":"Kittipeerapat N, Fabian R, Bernsen S et al (2023) Creatine kinase MB isoenzyme is a complementary biomarker in amyotrophic lateral sclerosis. Int J Mol Sci 24(14):11682. https:\/\/doi.org\/10.3390\/ijms241411682","journal-title":"Int J Mol Sci"},{"issue":"4","key":"12355_CR64","doi-asserted-by":"publisher","first-page":"fcab274","DOI":"10.1093\/braincomms\/fcab274","volume":"3","author":"S Castro-Gomez","year":"2021","unstructured":"Castro-Gomez S, Radermacher B, Tacik P et al (2021) Teaching an old dog new tricks: serum troponin T as a biomarker in amyotrophic lateral sclerosis. Brain Commun. 3(4):fcab274. https:\/\/doi.org\/10.1093\/braincomms\/fcab274","journal-title":"Brain Commun."}],"updated-by":[{"DOI":"10.1007\/s00415-024-12491-1","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2024,7,28]],"date-time":"2024-07-28T00:00:00Z","timestamp":1722124800000}}],"container-title":["Journal of Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12355-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00415-024-12355-8\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00415-024-12355-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T07:48:54Z","timestamp":1722239334000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00415-024-12355-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,29]]},"references-count":64,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2024,7]]}},"alternative-id":["12355"],"URL":"https:\/\/doi.org\/10.1007\/s00415-024-12355-8","relation":{"correction":[{"id-type":"doi","id":"10.1007\/s00415-024-12491-1","asserted-by":"object"}]},"ISSN":["0340-5354","1432-1459"],"issn-type":[{"value":"0340-5354","type":"print"},{"value":"1432-1459","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,29]]},"assertion":[{"value":"8 January 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"23 March 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 April 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 July 2024","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1007\/s00415-024-12491-1","URL":"https:\/\/doi.org\/10.1007\/s00415-024-12491-1","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Camilla Wohnrade received travel compensations from ITF Pharma GmbH outside the submitted work. Tabea Seeliger received financial support for conference attendance fees by Abbvie, honoraria for preparation of a manuscript by Springer and a research grant by Novartis Pharma GmbH outside the submitted work. Stefan Gingele received research support from Alnylam Pharmaceuticals, CSL Behring, Else Kr\u00f6ner Fresenius Foundation, Deutsche Forschungsgemeinschaft and Hannover Biomedical Research School (HBRS) and consulting and\/or speaker honoraria from Alexion, Alnylam Pharmaceuticals, AstraZeneca, GSK, Pfizer and Merck all outside the submitted work. Bogdan Bjelica received travel compensations from ITF pharma GmbH outside the submitted work. Thomas Skripuletz reports honoraria for lectures and travel expenses for attending meetings from Alexion, Alnylam Pharmaceuticals, argenx, Bayer Vital, Biogen, Celgene, Centogene, CSL Behring, Euroimmun, Grifols, Hexal AG, Janssen-Cilag, Merck Serono, Novartis, Pfizer, Roche, Sanofi, Siemens, Swedish Orphan Biovitrum, Teva, Viatris. His research is supported by the German Ministry for Education and Research (BMBF), Bristol-Myers Squibb Foundation for Immuno-Oncology, Claudia von Schilling Foundation for Breast Cancer Research, Else Kr\u00f6ner Fresenius Foundation, Hannover Biomedical Research School (HBRS), Alnylam Pharmaceuticals, CSL Behring, Novartis, Sanofi Genzyme, and VHV Foundation. Susanne Petri received honoraria as a speaker\/consultant from Biogen GmbH, Roche, Novartis, Teva, Cytokinetics Inc., Desitin, Italfarmaco, Zambon, Amylyx; and grants from DGM e.V, Federal Ministry of Education and Research, German Israeli Foundation for Scientific Research and Development, EU Joint Programme for Neurodegenerative Disease Research outside the submitted work.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"This investigation was approved by the Ethics Committee of Hannover Medical School (no. 8172-BO-K-2018 and no. 6269 2018) and has, therefore, been performed in accordance with the ethical standards laid down in the\u00a01964 Declaration of Helsinki\u00a0and its later amendments.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"All participants gave their written informed consent prior to their inclusion in the study.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent"}}]}}