Skip to main content
Top
Published in: Journal of Neurology 8/2020

01-08-2020 | Multiple Sclerosis | Original Communication

Longitudinal serum neurofilament light chain (sNfL) concentration relates to cognitive function in multiple sclerosis patients

Authors: Flavia Mattioli, F. Bellomi, C. Stampatori, S. Mariotto, S. Ferrari, S. Monaco, C. Mancinelli, R. Capra

Published in: Journal of Neurology | Issue 8/2020

Login to get access

Abstract

Background

Serum neurofilament light chain (sNfL) may be used as a biological marker of disease progression in multiple sclerosis (MS), although longitudinal studies correlating cognitive deficits to sNfL are limited.

Objective

To longitudinally investigate the relation between cognitive dysfunction, sNfL and MRI brain volume in a relapsing remitting MS patients.

Methods

18 MS patients (9 males and 9 females, mean age 45 years, mean education 12.6 years) all prescribed with interferon beta 1a (44 mcg 3 times per week), are longitudinally evaluated by means of annual clinical exam with EDSS, neuropsychological evaluation with Brief repeatable battery (BRB) and Delis Kaplan Executive function test (DKEFS), dosage of sNfL (SIMOA) and MRI.

Results

Here are reported the results of 1 year follow-up. A significantly higher sNfL in MS compared to healthy controls and higher sNfL in patients with greater cognitive impairment were found. Cognitive Impairment Index, memory, executive function tests correlated with sNfL. Gray matter volume resulted unchanged at 1-year follow-up; a weak correlation between some tests’ score and selective cortical brain areas was found.

Conclusion

Our longitudinal pilot study confirms that sNfL are related to cognitive abilities, confirming data of other authors from retrospective studies.
Literature
1.
go back to reference Benedict RH, Zivadinov R (2011) Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 7(6):332CrossRef Benedict RH, Zivadinov R (2011) Risk factors for and management of cognitive dysfunction in multiple sclerosis. Nat Rev Neurol 7(6):332CrossRef
2.
go back to reference Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7(12):1139–1151CrossRef Chiaravalloti ND, DeLuca J (2008) Cognitive impairment in multiple sclerosis. Lancet Neurol 7(12):1139–1151CrossRef
4.
go back to reference Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, Cilia S, Gallo P, Grossi P, Ghezzi A, Roscio M (2017) Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler J 23(9):1258–1267CrossRef Ruano L, Portaccio E, Goretti B, Niccolai C, Severo M, Patti F, Cilia S, Gallo P, Grossi P, Ghezzi A, Roscio M (2017) Age and disability drive cognitive impairment in multiple sclerosis across disease subtypes. Mult Scler J 23(9):1258–1267CrossRef
5.
go back to reference Portaccio E, Stromillo ML, Goretti B, Zipoli V, Siracusa G, Battaglini M, Giorgio A, Bartolozzi ML, Guidi L, Sorbi S, Federico A (2009) Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis. Neurology 73(7):498–503CrossRef Portaccio E, Stromillo ML, Goretti B, Zipoli V, Siracusa G, Battaglini M, Giorgio A, Bartolozzi ML, Guidi L, Sorbi S, Federico A (2009) Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis. Neurology 73(7):498–503CrossRef
6.
go back to reference Ruano L, Branco M, Portaccio E, Goretti B, Niccolai C, Patti F, Chisari C, Gallo P, Grossi P, Ghezzi A, Roscio M (2018) Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study. Mult Scler J 24(9):1234–1242CrossRef Ruano L, Branco M, Portaccio E, Goretti B, Niccolai C, Patti F, Chisari C, Gallo P, Grossi P, Ghezzi A, Roscio M (2018) Patients with paediatric-onset multiple sclerosis are at higher risk of cognitive impairment in adulthood: an Italian collaborative study. Mult Scler J 24(9):1234–1242CrossRef
9.
go back to reference Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, Alvarez-Cermeño JC, Andreasson U, Axelsson M, Bäckström DC, Bartos A, Bjerke M (2019) Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. JAMA Neurol 76:1035CrossRef Bridel C, van Wieringen WN, Zetterberg H, Tijms BM, Teunissen CE, Alvarez-Cermeño JC, Andreasson U, Axelsson M, Bäckström DC, Bartos A, Bjerke M (2019) Diagnostic value of cerebrospinal fluid neurofilament light protein in neurology: a systematic review and meta-analysis. JAMA Neurol 76:1035CrossRef
10.
go back to reference Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, Koel-Simmelink MJ, Schepens M, Bouwman F, Twaalfhoven HA, Blom HJ, Jakobs CA (2009) Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 72(15):1322–1329CrossRef Teunissen CE, Iacobaeus E, Khademi M, Brundin L, Norgren N, Koel-Simmelink MJ, Schepens M, Bouwman F, Twaalfhoven HA, Blom HJ, Jakobs CA (2009) Combination of CSF N-acetylaspartate and neurofilaments in multiple sclerosis. Neurology 72(15):1322–1329CrossRef
11.
go back to reference 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(5):703–712CrossRef 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(5):703–712CrossRef
12.
go back to reference Martin SJ (2019) CSF neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case control studies. J Neurol Neurosurg Psychiatry 24:1059CrossRef Martin SJ (2019) CSF neurofilament light chain in multiple sclerosis and its subtypes: a meta-analysis of case control studies. J Neurol Neurosurg Psychiatry 24:1059CrossRef
13.
go back to reference Kuhle J, Disanto G, Lorscheider J, Stites T, Chen Y, Dahlke F, Francis G, Shrinivasan A, Radue EW, Giovannoni G, Kappos L (2015) Fingolimod and CSF neurofilament light chain levels in relapsing–remitting multiple sclerosis. Neurology 84(16):1639–1643CrossRef Kuhle J, Disanto G, Lorscheider J, Stites T, Chen Y, Dahlke F, Francis G, Shrinivasan A, Radue EW, Giovannoni G, Kappos L (2015) Fingolimod and CSF neurofilament light chain levels in relapsing–remitting multiple sclerosis. Neurology 84(16):1639–1643CrossRef
14.
go back to reference Hendricks R, Baker D, Brumm J, Davancaze T, Harp C, Herman A, Büdingen HC, Townsend M, Fischer SK (2019) Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood. Bioanalysis 11(15):1405–1418CrossRef Hendricks R, Baker D, Brumm J, Davancaze T, Harp C, Herman A, Büdingen HC, Townsend M, Fischer SK (2019) Establishment of neurofilament light chain Simoa assay in cerebrospinal fluid and blood. Bioanalysis 11(15):1405–1418CrossRef
15.
go back to reference Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, Leppert D, Gobbi C, Granziera C, Yaldizli Ö, Michalak Z (2018) Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 141(8):2382–2391CrossRef Barro C, Benkert P, Disanto G, Tsagkas C, Amann M, Naegelin Y, Leppert D, Gobbi C, Granziera C, Yaldizli Ö, Michalak Z (2018) Serum neurofilament as a predictor of disease worsening and brain and spinal cord atrophy in multiple sclerosis. Brain 141(8):2382–2391CrossRef
16.
go back to reference Jakimowski D, Zivadinov R, Ramantam N, Hagemejer J, Weinstock-Guttman B, Tomic D, Kropshofer H, Fuchs TA, Barro C, Leppert D, Yaldizli O, Khule J, Benedict RHB (2019) Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: a longitudinal retrospective 5-year study. Mult Scler J Jakimowski D, Zivadinov R, Ramantam N, Hagemejer J, Weinstock-Guttman B, Tomic D, Kropshofer H, Fuchs TA, Barro C, Leppert D, Yaldizli O, Khule J, Benedict RHB (2019) Serum neurofilament light chain level associations with clinical and cognitive performance in multiple sclerosis: a longitudinal retrospective 5-year study. Mult Scler J
17.
go back to reference Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–30217CrossRef Polman CH, Reingold SC, Banwell B et al (2011) Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol 69(2):292–30217CrossRef
18.
go back to reference Amato MP, Portaccio E, Goretti B, Zipoli V, Ricchiuti L, De Caro MF, Patti F, Vecchio R, Sorbi S, Trojano M (2006) The Rao’s Brief Repeatable Battery and Stroop Test: normative values with age, education and gender corrections in an Italian population. Mult Scler J 12(6):787–793CrossRef Amato MP, Portaccio E, Goretti B, Zipoli V, Ricchiuti L, De Caro MF, Patti F, Vecchio R, Sorbi S, Trojano M (2006) The Rao’s Brief Repeatable Battery and Stroop Test: normative values with age, education and gender corrections in an Italian population. Mult Scler J 12(6):787–793CrossRef
19.
go back to reference Goretti B, Patti F, Cilia S, Mattioli F, Stampatori C, Scarpazza C, Portaccio E (2014) The Rao’s Brief Repeatable Battery version B: normative values with age, education and gender corrections in an Italian population. Neurol Sci 35(1):79–82CrossRef Goretti B, Patti F, Cilia S, Mattioli F, Stampatori C, Scarpazza C, Portaccio E (2014) The Rao’s Brief Repeatable Battery version B: normative values with age, education and gender corrections in an Italian population. Neurol Sci 35(1):79–82CrossRef
20.
go back to reference Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Galli P, Guarneri C, Corso B, Montomoli C, Niccolai C, Goretti B, Amato MP (2014) Assessing executive function with the D-KEFS sorting test: normative data for a sample of the Italian adult population. Neurol Sci 35(12):1895–1902CrossRef Mattioli F, Stampatori C, Bellomi F, Scarpazza C, Galli P, Guarneri C, Corso B, Montomoli C, Niccolai C, Goretti B, Amato MP (2014) Assessing executive function with the D-KEFS sorting test: normative data for a sample of the Italian adult population. Neurol Sci 35(12):1895–1902CrossRef
21.
go back to reference Anderson AM, Easley KA, Kasher N, Franklin D, Heaton RK, Zetterberg H, Blennow K, Gisslen M, Letendre SL (2018) Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy. J Neurovirol 24(6):695–701CrossRef Anderson AM, Easley KA, Kasher N, Franklin D, Heaton RK, Zetterberg H, Blennow K, Gisslen M, Letendre SL (2018) Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy. J Neurovirol 24(6):695–701CrossRef
22.
go back to reference Quintana E, Coll C, Salavedra-Pont J et al (2018) Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain. Eur J Neurol 25(9):1189–1191CrossRef Quintana E, Coll C, Salavedra-Pont J et al (2018) Cognitive impairment in early stages of multiple sclerosis is associated with high cerebrospinal fluid levels of chitinase 3-like 1 and neurofilament light chain. Eur J Neurol 25(9):1189–1191CrossRef
23.
go back to reference Disanto G, Barro C, Benkert P et al (2017) Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870CrossRef Disanto G, Barro C, Benkert P et al (2017) Serum neurofilament light: a biomarker of neuronal damage in multiple sclerosis. Ann Neurol 81:857–870CrossRef
Metadata
Title
Longitudinal serum neurofilament light chain (sNfL) concentration relates to cognitive function in multiple sclerosis patients
Authors
Flavia Mattioli
F. Bellomi
C. Stampatori
S. Mariotto
S. Ferrari
S. Monaco
C. Mancinelli
R. Capra
Publication date
01-08-2020
Publisher
Springer Berlin Heidelberg
Published in
Journal of Neurology / Issue 8/2020
Print ISSN: 0340-5354
Electronic ISSN: 1432-1459
DOI
https://doi.org/10.1007/s00415-020-09832-1

Other articles of this Issue 8/2020

Journal of Neurology 8/2020 Go to the issue

Pioneers in Neurology

Wiktor Stein (1899–1979)