Serum and CSF neurofilament light chain levels in antibody-mediated encephalitis
- 55 Downloads
Circulating and cerebrospinal fluid (CSF) neurofilament light chain (NfL) levels represent a reliable indicator of disease activity and axonal damage in different neuroinflammatory conditions. Recently, high CSF NfL levels have been detected in active autoimmune encephalitis, as opposed to significant lower levels after clinical improvement. The aim of the present study was to evaluate serum and CSF NfL concentration in patients with autoimmune encephalitis and to analyse the association between NfL levels and clinical, MRI, and CSF data. We retrospectively included 25 patients with neurological syndromes associated with autoantibodies to neuronal cell surface antigens and we collected clinical, MRI, CSF, and follow-up data. Using an ultrasensitive method (Simoa, Quanterix), we measured NfL levels in serum and CSF samples of all patients and in 25 sera of healthy controls. Serum NfL levels were higher in all cases, including 20 patients with inflammatory MRI/CSF features and 5 non-inflammatory cases (median 16.9 pg/ml, range 4.5–90) than in controls (median 6.9 pg/ml, range 2.7–12.8; p < 0.001). A correlation between serum and CSF NfL levels was found (r = 0.461, p = 0.023), whereas no significant association was observed between NfL levels and clinical, MRI/CSF inflammatory burden, and antibody type. In the 13 available follow-up samples, correlation between disease activity and NfL values was also observed. In conclusion, NfL levels are significantly increased in the serum of patients with antibody-mediated encephalitis, independently of the MRI/CSF inflammatory profile. These findings support the presence of ongoing axonal damage and suggest the co-occurrence of different mechanisms for neuronal/axonal involvement in antibody-associated CNS syndromes.
KeywordsNeurofilament light chain NfL Autoimmune encephalitis NMDAR LGI1 CASPR2
This work was supported by the Ministry of Health (RF-2011-0234-7955).
Compliance with ethical standards
Conflicts of interest
Sa.Ma. was sponsored by Merck for attending a scientific meeting. AG received research support funding from Merck. Sa.Mo. received honoraria from Biogen. S.F. was sponsored by Shire for attending a scientific meeting. The other authors declare that they have no conflict of interest.
All human studies have been performed in accordance with the ethical standards laid down in the 1964 declaration of Helsinki and its later amendments.
We collected consented to diagnostic procedures and biological sample storage at the referring laboratory for research use from all patients or legal representatives.
- 1.Gaiottino J, Norgren N, Dobson R, Topping J, Nissim A, Malaspina A, Bestwick JP, Monsch AU, Regeniter A, Lindberg RL, Kappos L, Leppert D, Petzold A, Giovannoni G, Kuhle J (2013) Increased neurofilament light chain blood levels in neurodegenerative neurological diseases. PLoS One 8:e75091CrossRefGoogle Scholar
- 3.Byrne LM, Rodrigues FB, Blennow K, Durr A, Leavitt BR, Roos RAC, Scahill RI, Tabrizi SJ, Zetterberg H, Langbehn D, Wild EJ (2017) Neurofilament light protein in blood as a potential biomarker of neurodegeneration in Huntington’s disease: a retrospective cohort analysis. Lancet Neurol 16:601–609CrossRefGoogle Scholar
- 5.Rohrer JD, Woollacott IO, Dick KM, Brotherhood E, Gordon E, Fellows A, Toombs J, Druyeh R, Cardoso MJ, Ourselin S, Nicholas JM, Norgren N, Mead S, Andreasson U, Blennow K, Schott JM, Fox NC, Warren JD, Zetterberg H (2016) Serum neurofilament light chain protein is a measure of disease intensity in frontotemporal dementia. Neurology 87:1329–1336CrossRefGoogle Scholar
- 6.Gille B, De Schaepdryver M, Goossens J, Dedeene L, De Vocht J, Oldoni E, Goris A, Van Den Bosch L, Depreitere B, Claeys KG, Tournoy J, Van Damme P, Poesen K (2018) Serum neurofilament light chain levels as a marker of upper motor neuron degeneration in patients with amyotrophic lateral sclerosis. Neuropathol Appl Neurobiol. https://doi.org/10.1111/nan.12511 Google Scholar
- 8.Mariotto S, Farinazzo A, Monaco S, Gajofatto A, Zanusso G, Schanda K, Capra R, Mancinelli C, Bonora A, Bombardi R, Reindl M, Ferrari S (2017) Serum neurofilament light chain in NMOSD and related disorders: comparison according to aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies status. Mult Scler J Exp Transl Clin 3:2055217317743098Google Scholar
- 9.Kuhle J, Barro C, Disanto G, Mathias A, Soneson C, Bonnier G, Yaldizli Ö, Regeniter A, Derfuss T, Canales M, Schluep M, Du Pasquier R, Krueger G, Granziera C (2016) Serum neurofilament light chain in early relapsing remitting MS is increased and correlates with CSF levels and with MRI measures of disease severity. Mult Scler 22:1550–1559CrossRefGoogle Scholar
- 12.Disanto G, Barro C, Benkert P, Naegelin Y, Schädelin S, Giardiello A, Zecca C, Blennow K, Zetterberg H, Leppert D, Kappos L, Gobbi C, Kuhle J, Swiss Multiple Sclerosis Cohort Study Group (2017) Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870CrossRefGoogle Scholar
- 13.Håkansson I, Tisell A, Cassel P, Blennow K, Zetterberg H, Lundberg P, Dahle C, Vrethem M, Ernerudh J (2017) Neurofilament light chain in cerebrospinal fluid and prediction of disease activity in clinically isolated syndrome and relapsing-remitting multiple sclerosis. Eur J Neurol 24:703–712CrossRefGoogle Scholar
- 16.Constantinescu R, Krýsl D, Bergquist F, Andrén K, Malmeström C, Asztély F, Axelsson M, Menachem EB, Blennow K, Rosengren L, Zetterberg H (2016) Cerebrospinal fluid markers of neuronal and glial cell damage to monitor disease activity and predict long-term outcome in patients with autoimmune encephalitis. Eur J Neurol 23:796–806CrossRefGoogle Scholar
- 17.Constantinescu R, Krýsl D, Andrén K, Asztély F, Bergquist F, Zetterberg H, Andreasson U, Axelsson M, Menachem EB, Jons D, Mahamud U, Malmeström C, Rosengren L, Blennow K (2017) Cerebrospinal fluid markers of neuronal and glial cell damage in patients with autoimmune neurologic syndromes with and without underlying malignancies. J Neuroimmunol 306:25–30CrossRefGoogle Scholar
- 21.Finke C, Kopp UA, Scheel M, Pech LM, Soemmer C, Schlichting J, Leypoldt F, Brandt AU, Wuerfel J, Probst C, Ploner CJ, Prüss H, Paul F (2013) Functional and structural brain changes in anti-N-methyl-d-aspartate receptor encephalitis. Ann Neurol 74:284–296Google Scholar
- 22.Irani SR, Bera K, Waters P, Zuliani L, Maxwell S, Zandi MS, Friese MA, Galea I, Kullmann DM, Beeson D, Lang B, Bien CG, Vincent A (2010) N-methyl-d-aspartate antibody encephalitis: temporal progression of clinical and paraclinical observations in a predominantly non-paraneoplastic disorder of both sexes. Brain 133:1655–1667CrossRefGoogle Scholar
- 24.Titulaer MJ, McCracken L, Gabilondo I, Armangué T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J (2013) Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol 12:157–165CrossRefGoogle Scholar
- 27.Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, Leppert D, Gobbi C, Granziera C, Yaldizli Ö, Michalak Z, Wuerfel J, Kappos L, Parmar K, Kuhle J (2018) Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 141:2382–2391CrossRefGoogle Scholar