#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Neurofilament light chains in serum and cerebrospinal fluid and status of blood-CSF bar­rier in the selected neurological dis­eases


Authors: L. Fialová 1;  A. Bartoš 2,3;  J. Švarcová 4
Authors‘ workplace: Ústav lékařské biochemie a laboratorní diagnostiky, 1. LF UK a VFN v Praze 1;  Národní ústav duševního zdraví, Klecany 2;  Neurologická klinika 3. LF UK a FN Královské Vinohrady, Praha 3;  Ústav lékařské chemie a klinické biochemie, 2. LF UK a FN Motol, Praha 4
Published in: Cesk Slov Neurol N 2018; 81(2): 185-192
Category: Original Paper
doi: https://doi.org/10.14735/amcsnn2018185

Overview

Aim:
The aim of this study was to assess the relationship between blood-CSF barrier permeability evaluated by the albumin quotient (Qalb) and levels of neurofilament light chains (NFL) in serum and cerebrospinal fluid (CSF) in several groups of neurological patients with a different degree of the impairment of blood-CSF barrier.

Materials and methods:
The total number of 137 participants included 50 patients with multiple sclerosis with the inclusion of clinically isolated syndrome, 24 patients with Alzheimer’s disease, 17 patients with aseptic neuroinfections, 36 patients with various non-inflammatory neurological diseases and 10 symptomatic controls. Serum and CSF NFL levels were determined by the ELISA method. Serum and CSF albumin levels were tested by immunonephelometry. Qalb was calculated as a ratio of CSF/ serum albumin levels.

Results:
No positive correlations between serum NFL levels and Qalb values were found in the tested patients’ groups. CSF NFL levels were positively correlated with Qalb values in patients with neuroinfections and in patients with non-inflammatory neurological diseases. A positive correlation between serum NFL levels and those in CSF was found in patients with aseptic neuroinfections even when patients were evaluated as a whole.

Conclusions:
Serum NFL levels do not seem to be directly influenced by blood-CSF barrier permeability assessed by Qalb in neurodegenerative diseases and neuroinfections. On the contrary, the relationship between CSF NFL levels and Qalb may be affected by the characteristics of the neuropathological changes in individual neurological diseases.

Key words:
albumin quotient – Alzheimer´s disease – cytoskeleton – blood-CSF barrier – multiple sclerosis – neuroinfection – neurofilaments

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscript met the ICMJE “uniform requirements” for biomedical papers.


Sources

1. Gotow T. Neurofilaments in health and dis­ease. Med Electron Microsc 2000; 33(4): 173– 199.

2. Hjalmars­son C, Bjerke M, Anders­son B et al. Neuronal and glia-related bio­markers in cerebrospinal fluid of patients with acute ischemic stroke. J Cent Nerv Syst Dis 2014; 6: 51– 58. doi: 10.4137/ JCNSD.S13821.

3. Fialova L, Malbohan I. Neuronal cytoskeleton components in cerebrospinal fluid in selected neurological diseases. In Slavik V, Dolezal T (eds). Cerebrospinal fluid: functions, composition and disorders. New York: Nova Science Publishers 2012; 65– 86.

4. Piťha J. Biomarkery roztroušené sklerózy – současné možnosti a perspektivy. Cesk Slov Neurol N 2015; 78/ 111(3): 269– 273.

5. Fialova L, Bartos A, Svarcova J et al. Serum and cerebrospinal fluid light neurofilaments and antibodies against them in clinical­ly isolated syndrome and multiple sclerosis. J Neuroim­munol 2013; 262(1– 2): 113– 120. doi: 10.1016/ j.jneuroim.2013.06.010.

6. Teunis­sen CE, Iacobaeus E, Khademi M et al. Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 2009; 72(15): 1322– 1329. doi: 10.1212/ WNL.0b013e3181a0fe3f.

7. Norgren N, Rosengren L, Stigbrand T. Elevated neurofilament levels in neurological dis­eases. Brain Res 2003; 987(1): 25– 31.

8. Disanto G, Adiutori R, Dobson R et al. Serum neurofilament light chain levels are increased in patients with a clinical­ly isolated syndrome. J Neurol Neurosurg Psychiatry 2016; 87(2): 126– 129. doi: 10.1136/ jn­np-2014-309690.

9. Matts­son N, Andreas­son U, Zetterberg H et al. As­sociation of plasma neurofilament light with neurodegeneration in patients with Alzheimer dis­ease. JAMA Neurol 2017; 74(5): 557– 566. doi: 10.1001/ jamaneurol.2016.6117.

10. Kuhle J, Bar­ro C, Disanto G et al. 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 2016; 22(12): 1550– 1559.

11. Kuhle J, Bar­ro C, Andreas­son U et al. Comparison of three analytical platforms for quantification of the neurofilament light chain in blood samples: ELISA, electrochemiluminescence im­munoas­say and Simoa. Clin Chem Lab Med 2016; 54(10): 1655– 1661. doi: 10.1515/ cclm-2015-1195.

12. Fialova L, Bartos A, Svarcova J. Neurofilaments and tau proteins in cerebrospinal fluid and serum in dementias and neuroinflam­mation. Biomed Pap MedFac Univ Palacky Olomouc Czech Repub 2017; 161(3): 286– 295. doi: 10.5507/ bp.2017.038.

13. Havrdová E. Roztroušená skleróza. Cesk Slov Neurol N 2008; 71/ 104(2): 121– 132.

14. Friese MA, Schattl­­ing B, Fugger L. Mechanisms of neurodegeneration and axonal dysfunction in multiple sclerosis. Nat Rev Neurol 2014; 10(4): 225– 238. doi: 10.1038/ nrneurol.2014.37.

15. Mareš J. Význam časné dia­gnostiky a terapie v životní perspektivě pa­cientů s roztroušenou sklerózou. Med praxi 2013; 10(4): 149– 153.

16. Disanto G, Bar­ro C, Benkert P et al. Serum Neurofilament light: a bio­marker of neuronal damage in multiple sclerosis. Ann Neurol 2017; 81(6): 857– 870. doi: 10.1002/ ana.24954.

17. Khalil M, Enzinger C, Langkam­mer C et al. CSF neurofilament and N-acetylaspartate related brain changes in clinical­ly isolated syndrome. Mult Scler 2013; 19(4): 436– 442. doi: 10.1177/ 1352458512458010.

18. Rektorová I. Neurodegenerativní demence. Cesk Slov Neurol N 2009; 72/ 105(2): 97–  109.

19. Yuan A, Nixon RA. Specialized roles of neurofilament proteins in synapses: Relevance to neuropsychiatric disorders. Brain Res Bull 2016; 126(Pt 3): 334– 346. doi: 10.1016/ j.brainresbul­l.2016.09.002.

20. Bartoš A, Čechová L, Švarcová J et al. Likvorový triplet (tau proteiny a beta-amyloid) v dia­gnostice Alzheimerovy-Fischerovy nemoci. Cesk Slov Neurol N 2012; 75/ 108(5): 587– 594.

21. Ols­son B, Lautner R, Andreas­son U et al. CSF and blood bio­markers for the dia­gnosis of Alzheimer‘s dis­ease: a systematic review and meta-analysis. Lancet Neurol 2016; 15(7): 673– 684. doi: 10.1016/ S1474-4422(16)00070-3.

22. Bacioglu M, Maia LF, Preische O et al. Neurofilament light chain in blood and CSF as marker of dis­ease progres­sion in mouse models and in neurodegenerative dis­eases. Neuron 2016; 91(2): 494– 496. doi: 10.1016/ j.neuron.2016.07.007.

23. Piťha J. Bariéry nervového systému za fyziologických a patologických stavů. Cesk Slov Neurol N 2014; 77/ 110(5): 553– 559.

24. Brettschneider J, Claus A, Kas­subek J et al. Isolated blood-cerebrospinal fluid bar­rier dysfunction: prevalence and as­sociated dis­eases. J Neurol 2005; 252(9): 1067– 1073.

25. Kalm M, Boström M, Sandelius A et al. Serum concentrations of the axonal injury marker neurofilament light protein are not influenced by blood-brain bar­rier permeability. Brain Res 2017; 1668: 12– 19. doi: 10.1016/ j.brainres.2017.05.011.

26. Polman CH, Reingold SC, Edan G et al. Dia­gnostic criteria for multiple sclerosis: 2005 revisions to the „McDonald Criteria“. Ann Neurol 2005; 58(6): 840– 846.

27. McKhann GM, Knopman DS, Chertkow H et al. The dia­gnosis of dementia due to Alzheimer‘s dis­ease: recom­mendations from the National Institute on Aging-Alzheimer‘s As­sociation workgroups on dia­gnostic guide­lines for Alzheimer‘s dis­ease. Alzheimers Dement 2011; 7(3): 263– 269. doi: 10.1016/ j.jalz.2011.03.005.

28. Mioshi E, Dawson K, Mitchell J et al. The Addenbrooke‘s Cognitive Examination Revised (ACE-R): a brief cognitive test battery for dementia screening. Int J Geriatr Psychiatry 2006; 21(11): 1078– 1085.

29. Bartoš A, Raisová M and Kopeček M. Amendment of the Czech Addenbrooke’s cognitive examination (ACE-CZ). Cesk Slov Neurol N 2011; 74/ 107(6): 681– 684.

30. Bartoš A, Raisová M and Kopeček M. Důvody a průběh novelizace české verze Addenbrookského kognitivního testu (ACE-CZ). Cesk Slov Neurol N 2011; 74/ 107(6): e1– e5.

31. Scheltens P, Leys D, Barkhof F et al. Atrophy of medial temporal lobes on MRI in „probable“ Alzheimer‘s dis­ease and normal ageing: dia­gnostic value and neuropsychological cor­relates. J Neurol Neurosurg Psychiatry 1992; 55(10): 967– 972.

32. Bartoš A, Zach P, Diblíková F et al. Visual rat­­ing of medial temporal lobe atrophy on magnetic resonance imag­­ing in Alzheimer’s dis­ease. Psychiatrie 2007; 11 (Suppl 3): 49– 52.

33. Teunis­sen C, Menge T, Altintas A et al. Consensus definitions and application guidelines for control groups in cerebrospinal fluid bio­marker studies in multiple sclerosis. Mult Scler 2013; 19(13): 1802–1809. doi: 10.1177/ 1352458513488232.

34. Zima T. Laboratorní dia­gnostika. 3. doplněné a přepracované vydání. Praha: Galén 2013.

35. Deisenham­mer F, Bartos A, Egg R et al. Guidelines on routine cerebrospinal fluid analysis. Report from an EFNS task force. Eur J Neurol 2006; 13(9): 913– 922.

36. Teunis­sen CE, Petzold A, Ben­nett JL et al. A consensus protocol for the standardization of cerebrospinal fluid col­lection and bio­banking. Neurology 2009; 73(22): 1914– 1922. doi: 10.1212/ WNL.0b013e3181c47cc2.

37. LeVine SM. Albumin and multiple sclerosis. BMC Neurol 2016; 16: 47. doi: 10.1186/ s12883-016-0564-9.

38. Schenk GJ, de Vries HE. Altered blood-brain bar­rier transport in neuro-inflam­matory disorders. Drug Discov Today Technol 2016; 20: 5– 11. doi: 10.1016/ j.ddtec.2016.07.002.

39. Uher T, Horakova D, Tyblova M et al. Increased albumin quotient (QAlb) in patients after first clinical event suggestive of multiple sclerosis is as­sociated with development of brain atrophy and greater disability 48 months later. Mult Scler 2016; 22(6): 770– 781. doi: 10.1177/ 1352458515601903.

40. Bednarova J. Cerebrospinal-fluid profile in neurobor­reliosis and its dia­gnostic significance. Folia Microbio­l (Praha) 2006; 51(6): 599– 603.

41. Kawata K, Liu CY, Merkel SF et al. Blood bio­markers for brain injury: What are we measuring? Neurosci Biobehav Rev 2016; 68: 460– 473. doi: 10.1016/ j.neubio­rev.2016.05.009.

42. Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clin Chim Acta 2001; 310(2): 173– 186.

43. Reiber H. Proteins in cerebrospinal fluid and blood: bar­riers, CSF flow rate and source-related dynamics. Restor Neurol Neurosci 2003; 21(3– 4): 79– 96.

44. Shaw G. The use and potential of pNF-H as a general blood biomarker of axonal los­s: an im­mediate application for CNS injury. In: Kobeis­sy FH. Brain neurotrauma: molecular, neuropsychological, and rehabilitation aspects. Boca Raton (FL): CRC Pres­s/ Taylor & Francis, 2015.

45. Anesten B, Yilmaz A, Hagberg L et al. Blood-brain bar­rier integrity, intrathecal im­munoactivation, and neuronal injury in HIV. Neurol Neuroim­munol Neuroinflamm 2016; 3(6): e300.

46. Sus­smuth SD, Reiber H, Tumani H. Tau protein in cerebrospinal fluid (CSF): a blood-CSF bar­rier related eval­uation in patients with various neurological dis­eases. Neurosci Lett 2001; 300(2): 95– 98.

47. Liguori C, Olivola E, Pierantozzi M et al. Cerebrospinal-fluid Alzheimer‘s dis­ease biomarkers and blood-brain bar­rier integrity in a natural population of cognitive intact Parkinson‘s dis­ease patients. CNS Neurol Disord Drug Targets 2017; 16(3): 339– 345. doi: 10.2174/ 1871527316666161205123123.

48. Kuhle J, Leppert D, Petzold A et al. Neurofilament heavy chain in CSF cor­relates with relapses and disability in multiple sclerosis. Neurology 2011; 76(14): 1206– 1213. doi: 10.1212/ WNL.0b013e31821432f­f.

49. Gaiottino J, Norgren N, Dobson R et al. Increased neurofilament light chain blood levels in neurodegenerative neurological dis­eases. PLoS One 2013; 8(9): e75091. doi: 10.1371/ journal.pone.0075091.

Labels
Paediatric neurology Neurosurgery Neurology

Article was published in

Czech and Slovak Neurology and Neurosurgery

Issue 2

2018 Issue 2

Most read in this issue
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#