
==== Front
Blood Cancer J
Blood Cancer J
Blood Cancer Journal
2044-5385
Nature Publishing Group UK London

39237493
1118
10.1038/s41408-024-01118-3
Correspondence
Blood neurofilament light chain measurements in adults with CNS histiocytic neoplasms
http://orcid.org/0000-0002-5856-1367
Banks Samantha A. 1
Decker Paul 2
Flanagan Eoin P. 134
Zekeridou Anastasia 134
http://orcid.org/0000-0002-8284-3495
Go Ronald S. 5
http://orcid.org/0000-0003-3939-6252
Abeykoon Jithma P. 5
Goyal Gaurav 6
http://orcid.org/0000-0001-5351-8266
Young Jason R. 7
Koster Matthew J. 8
http://orcid.org/0000-0003-2328-0255
Vassallo Robert 9
http://orcid.org/0000-0002-9576-2272
Ryu Jay H. 9
Davidge-Pitts Caroline J. 10
Ravindran Aishwarya 11
Sartori Valinotti Julio C. 12
http://orcid.org/0000-0001-8358-5953
Bennani N. Nora 5
http://orcid.org/0000-0002-5359-336X
Shah Mithun V. 5
http://orcid.org/0000-0001-6770-2339
Rech Karen L. 13
Bach Corrie R. 7
Eckel-Passow Jeanette E. 2
http://orcid.org/0000-0002-8141-2394
Tobin W. Oliver tobin.oliver@mayo.edu

14
the Mayo Clinic-University of Alabama at Birmingham Histiocytosis Working Group and Center for Multiple Sclerosis and Autoimmune Neurology at Mayo Clinic
1 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Department of Neurology, Mayo Clinic, Rochester, MN USA
2 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Department of Quantitative Health Sciences, Mayo Clinic, Rochester, MN USA
3 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Department of Laboratory medicine and Pathology, Mayo Clinic, Rochester, MN USA
4 grid.66875.3a 0000 0004 0459 167X Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology, Rochester, MN USA
5 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Division of Hematology, Mayo Clinic, Rochester, MN USA
6 https://ror.org/008s83205 grid.265892.2 0000 0001 0634 4187 Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, AL USA
7 grid.417467.7 0000 0004 0443 9942 Department of Radiology, at Mayo Clinic in Jacksonville, Jacksonville, FL USA
8 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Division of Rheumatology, Mayo Clinic, Rochester, MN USA
9 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, MN USA
10 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Division of Endocrinology, Diabetes, and Nutrition, Mayo Clinic, Rochester, MN USA
11 https://ror.org/008s83205 grid.265892.2 0000 0001 0634 4187 Division of Laboratory Medicine-Hematopathology, Department of Pathology, University of Alabama at Birmingham, Birmingham, AL USA
12 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Department of Dermatology, Mayo Clinic, Rochester, MN USA
13 https://ror.org/02qp3tb03 grid.66875.3a 0000 0004 0459 167X Division of Hematopathology, Mayo Clinic, Rochester, MN USA
5 9 2024
5 9 2024
12 2024
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Subject terms

Translational research
Haematological cancer
https://doi.org/10.13039/100006108 U.S. Department of Health & Human Services | NIH | National Center for Advancing Translational Sciences (NCATS) UL1 TR002377 Banks Samantha A. issue-copyright-statement© Springer Nature Limited 2024
==== Body
pmcIntroduction

Histiocytic neoplasms constitute a group of rare hematologic neoplasms characterized by the accumulation of neoplastic histiocytic/dendritic cells with associated inflammatory infiltrate [1]. Central nervous system (CNS) involvement of these neoplasms is associated with increased morbidity and mortality [2, 3]. Contrast-enhanced brain and spine MRI is the current standard for evaluating for the presence of CNS disease and monitoring response to treatment [4]. Neurofilament light chain (NfL) is a recently identified biomarker of axonal degeneration that has been utilized in monitoring disease activity in a wide variety of neurologic diseases [5]. It has extensive potential clinical utility as it can be tested in blood. The aim of this study was to evaluate if elevated NfL in patients with histiocytic neoplasms is associated with CNS involvement and active CNS disease.

Methods

Ethics approval and consent to participate

This study was approved by the Institutional Review Board of Mayo Clinic, Rochester, Minnesota (Institutional Review Board 08-006647). All patients gave written consent to the use of medical records and blood samples for research purposes. All methods were performed in accordance with relevant guidelines and regulations.

Patient identification

All patients seen at Mayo Clinic, MN with a diagnosis of histiocytic disorder by biopsy and appropriate clinical phenotype who were enrolled in the Center for Multiple Sclerosis and Autoimmune Neurology (CMSAN) or Lymphoma Specialized Program of Research Excellence (SPORE) and had stored blood available were included. All cases were centrally reviewed by the Mayo Clinic-University of Alabama at Birmingham Histiocytosis Working Group to ensure appropriate classification [6]. Clinical data were abstracted by reviewing the electronic medical records and associated images.

Collection of clinical data

Medical records were reviewed by two neurologists (SAB and WOT). BRAF mutation status was tested as part of clinical care in 74 patients (multiple methods were used for testing in 27 patients) via immunohistochemistry in 44 patients, next-generation sequencing in 31 patients, cell-free DNA in 19, and digital droplet polymerase chain reaction in 5 patients. Parenchymal involvement of the brain and spinal cord was defined as T2 hyperintensity or gadolinium enhancement on MRI seen in the parenchyma of the brain and/or spinal cord, not better explained by another disease (eg. multiple sclerosis, non-specific leukoaraiosis). CNS involvement was defined as parenchymal brain or spinal involvement, enhancement of meninges or intracranial cranial nerve on post-gadolinium T1 MRI, and/or pituitary involvement by imaging or biochemical testing. Systemic involvement, including orbital, dermatologic, bone, renal, cardiac, and pulmonary, was noted. CSF analysis for oligoclonal bands was available in 18 of 27 patients; bands were considered positive if there were 2 or more CSF unique bands. Patients were evaluated for comorbidities that may impact NfL levels, including neurologic, cardiac [7, 8], and renal disease [9].

Neurofilament light-chain testing

Two different assays were used for neurofilament light-chain assessment. NfL was tested as part of clinical care in serum in 7 patients using the Simoa Quanterix assay with standardized levels determined by patient age [10]. In 76 patients with stored plasma available, NfL was tested using the Protein Simple Ella Simple Plex assay according to manufacturer protocol. Specifications provided by the manufacturer for the Ella NfL lab assay on serum provided a mean value of 10.6 pg/mL, standard deviation of 4.73 pg/mL, and a range of 6.23–22.2 pg/mL (n = 10). NfL values assessed by the SIMOA assay were transformed to the Ella assay as described previously (y = 2.97 + 1.61x) [11].

Radiographic review

Brain MRI was available in 26 of 27 (96%) (one patient had CT head) with CNS involvement, and spine was available in 18 of 27 (67%). Among those without CNS involvement, MRI brain was available in 38 of 56 (68%), and spine in 6 of 56 (10%). MRI of the brain with and without gadolinium was available for 23/27 (85%) patients within one month of the initial NfL blood sample draw (18 on 3 Tesla MRI, 5 on 1.5 Tesla MRI). Enhancement at the time of NfL was defined as parenchymal enhancement on post-gadolinium T1 images within 1 month of NfL test (Fig. 1).Fig. 1 Examples of MRI features evaluated and summary boxplots.

A, B T2 hyperintensity in bilateral middle cerebellar peduncles extending into cerebellum and pons (A, arrows) with associated gadolinium enhancement on T1 weighted images (B, arrows), defined as parenchymal brain involvement, with enhancement. C Gadolinium enhancement on T1 weighted images in subarachnoid spaces suggestive of leptomeningeal disease (C, arrow), defined in the study cohort as non-parenchymal CNS involvement, without parenchymal enhancement. D Large dural-based lesion with homogenous enhancement on T1 post-gadolinium sequences (D, arrow) with compression of brainstem and encasement of the vertebral artery, defined as non-parenchymal CNS involvement, without parenchymal enhancement. E Boxplot comparing cases to controls; neurofilament light chain (NfL) by Simoa assay transformed to Ella level plus Ella assay in patients with central nervous system (CNS) histiocytosis were significantly elevated compared to those with histiocytosis without CNS involvement (P < 0.0001). F NfL by Simoa assay transformed to Ella level plus Ella assay in patients with histiocytic disease without CNS involvement compared to those with CNS involvement with and without parenchymal involvement. NfL was significantly higher in those with parenchymal involvement than non-CNS histiocytosis (P < 0.0001). G NfL by Simoa assay transformed to Ella level plus Ella assay in patients with histiocytic disease without CNS involvement compared to those with CNS involvement with and without parenchymal enhancement. NfL was significantly higher in those with parenchymal enhancement than non-CNS histiocytosis (P < 0.0001).

Statistical analysis

Patient characteristics were compared across groups using the chi-square test for categorical variables and the Kruskal–Wallis test for continuous variables. Log transformations were performed as appropriate. In all analyses, P values < 0.05 were considered statistically significant.

Results

Demographic, clinical, and laboratory features

This cohort of 83 patients included 42 patients (51%) with ECD, 23 patients (28%) with LCH, 13 with RDD (16%), 2 with mixed ECD/RDD (2%), 2 with Histiocytic neoplasm (2%), and 1 with mixed LCH/ECD (1%). Patients with and without CNS histiocytosis did not differ significantly in demographic features or comorbidities (Supplemental Table 1). BRAF V600E mutation was present in 43% (32/74) in whom it was tested, including 54% of those with CNS involvement (14/26) and 38% without (18/48). Other mutations found in those with CNS involvement included: BRAF non-V600E mutations (2), CSF1R mutations (2), MAP2K1 mutation (1), NF1 loss of function (1), and GAB2-BRAF fusion (1). In those without CNS involvement, other mutations included: BRAF-LMTK2 fusion (1), UBR2-BRAF fusion (1), RNF1-BRAF fusion (1), MAP2K1 mutation (1), and PTPN11 gain of function (1).

CNS histiocytosis features

There was a median follow-up of 56 months (6–216) from neurologic symptom onset in those with CNS disease. MRI features are summarized in Supplemental Table 2. Oligoclonal bands were positive in CSF in 4/18 (22%). Systemic, non-CNS involvement was observed in 23/27 (85%) CNS histiocytosis patients including bone (14, 52%), renal (9, 33%), mediastinal or cardiac (4, 15%), vascular (4, 15%), pulmonary (4, 15%), lymph node (3, 11%), orbital (3, 11%), dermatologic (2, 7%), and gastrointestinal (2, 7%). Diabetes insipidus was found in 6 (22%), and anterior hypopituitarism in 4 (15%).

Neurofilament light chain in histiocytosis

The median NfL of 56 control patients with histiocytosis without CNS involvement was 17.8 pg/mL, (range 5.5–265.5 pg/mL). Patients with CNS histiocytic neoplasms had significantly higher NfL levels than those without CNS involvement regardless of assay used (Ella median 40.2 pg/mL, range 17.8–917.0; Ella assay plus Simoa corrected to Ella assay 47.3, range 15.2–917, P < 0.0001) (Table 1 and Fig. 1). Patients with parenchymal brain or spinal cord involvement had numerically higher NfL when compared with patients with CNS histiocytic neoplasms without parenchymal involvement (median parenchymal involvement 56.0 pg/mL, range 15.2–917.0; median without parenchymal involvement 37.0 pg/mL, range 17.8–167.2; P = 0.31) (Supplemental Table 3 and Fig. 1). Patients who had parenchymal enhancement on MRI within 1 month of NfL level testing had numerically higher NfL than those without enhancement (median parenchymal enhancement 56.0 pg/mL, range 17.8–917.0; median without parenchymal enhancement 38.2 pg/mL, range 15.2–86.0; P = 0.14) (Supplemental Table 4 and Fig. 1). One patient had multiple NfL measurements summarized in the Supplemental Figure.Table 1 Blood neurofilament light chain in CNS vs non-CNS histiocytosis.

NfL	All histiocytosis patients (n = 83)	CNS histiocytosis (n = 27)	Non-CNS histiocytosis (n = 56)	P valuea	
NfL by Ella assay, median (range) (pg/mL)	22.5 (5.5, 917.0)	40.2 (17.8, 917.0)	17.8 (5.5, 265.5)	<0.0001	
NfL by Ella assay AND Simoa, median (range) (pg/mL)	26.6 (5.5, 917.0)	47.3 (15.2, 917.0)	17.8 (5.5, 265.5)	<0.0001	
CNS central nervous system, NfL neurofilament light chain.

aKruskal–Wallis P value.

Discussion

This study demonstrates that NfL is a useful biomarker of active CNS histiocytic neoplasms. In this cohort of 83 patients with histiocytic neoplasms, NfL was significantly higher in patients with CNS involvement than those without. Further, in those with parenchymal disease and enhancement within 1 month of NfL measurement, NfL was numerically higher than in those without. Although this did not reach statistical significance, the magnitude of the difference was high.

This cohort of adult patients with histiocytosis predominantly included patients with ECD. BRAF V600E mutations were present in nearly half of those in whom it was tested in, and presence did not differ significantly between groups. Comorbidities known to impact NfL did not differ between the groups.

Current staging for CNS involvement of histiocytosis consists of neuraxial MRI scan with and without contrast. However, small lesions may go undetected, are difficult to monitor over time, and some patients cannot tolerate the MRI imaging. NfL is a readily available blood test that can be routinely measured on patients being monitored for and treated with histiocytosis. NfL has been studied in neurodegenerative and neuroinflammatory disorders and is a promising biomarker in histiocytic neoplasms. Previous work evaluating the utility of CSF NfL in 12 patients with LCH found levels to be elevated in half of the patients tested 4–12 years from disease onset, particularly in those with worsening radiographic features [12]. More recently, a study found CSF and plasma levels correlated in 10 patients with LCH [13]. The authors concluded that NfL could be a useful tool to screen for neurodegeneration. However, our study shows these values are most elevated in patients with actively enhancing radiographic disease, suggesting that NFL is most useful to identify and monitor active neoplasm in the CNS. A recent study evaluating Mitogen-activated protein kinase inhibitors for treatment of neurodegeneration using CSF NfL as a biomarker of treatment response in five children with LCH [14], found CSF NfL levels tended to decrease with treatment.

This study carries the limitations of a retrospective design. Two different assays were used as one was available on a research basis prior to commercial availability, though these assays have both been validated and directly compared [11], and the findings were supported in both assays. CNS involvement was defined by the presence of MRI changes and small lesions could have been missed. MRIs were not available in all the non-CNS histiocytosis cohort, however none had symptoms to suggest CNS involvement.

In conclusion, elevated blood NfL is a marker of neurologic involvement in histiocytic neoplasms and may represent a sensitive marker of active parenchymal disease. Further studies are needed to evaluate whether NfL can be used to monitor treatment response in patients with histiocytic neoplasms.

Supplementary information

List of consortium members

Supplemental Figure 1. Changes in neurofilament light chain change across a disease course in one patient.

Supplemental Figure. Changes in neurofilament light chain change across a disease course in one patient.

Supplemental Table 1. Demographic features and clinical features.

Supplemental Table 2. Radiographic features of patients with central nervous system involvement of histiocytosis

Supplemental Table 3. Blood neurofilament light chain test in CNS histiocytosis with and without parenchymal involvement.

Supplemental Table 4. Blood neurofilament light chain in CNS histiocytosis with and without MRI enhancement within one month.

Supplementary information

The online version contains supplementary material available at 10.1038/s41408-024-01118-3.

Acknowledgements

This publication was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS) and R01NS113803 from the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH. This work was made possible through the biospecimens made available in the Center for Multiple Sclerosis and Autoimmune Neurology (CMSAN) and Lymphoma Specialized Program of Research Excellence (SPORE).

Author contributions

SAB, PD, JEPE, and WOT were responsible for designing and reviewing the protocol. SAB, PD, JEPE, and WOT were responsible for writing the protocol and report. SAB and WOT were responsible for conducting research, extraction and analyzing data. SAB, EPF, AZ, RSG, JPA, GG, JRY, MJK, RV, JHR, CJDP, AR, JCSV, NNB, MVS, KLR, CRB, and WOT were responsible for reviewing cases and assigning accurate diagnoses. PD, EPF, AZ, RSG, JPA, GG, JRY, MJK, RV, JHR, CJDP, AR, JCSV, NNB, MVS, KLR, CRB, JEPE, and WOT provided feedback on the final report.

Data availability

Anonymized data used for this study are available on reasonable request to the corresponding author.

Competing interests

Dr. Banks was supported by Grant Number UL1 TR002377 from the National Center for Advancing Translational Sciences (NCATS), its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH; Dr Flanagan has served on advisory boards for Alexion, Genentech, Horizon Therapeutics and UCB. He has received research support from UCB, he has received speaker honoraria from Pharmacy Times, he received royalties from UpToDate, he is a site principal investigator in a randomized clinical trial of Rozanolixizumab for relapsing myelin oligodendrocyte glycoprotein antibody-associated disease run by UCB and is a site principal investigator and a member of the steering committee for a clinical trial of satralizumab for relapsing myelin oligodendrocyte glycoprotein antibody-associated disease run by Roche/Genentech, he has received funding from the NIH (R01NS113828), he is a member of the medical advisory board of the MOG project and is an editorial board member of Neurology, Neuroimmunology and Neuroinflammation, The Journal of the Neurological Sciences and Neuroimmunology Reports, a patent has been submitted on DACH1-IgG as a biomarker of paraneoplastic autoimmunity; Dr. Zekeridou reports patents submitted for PDE10A-IgG, DACH1-IgG and Tenascin-R-IgG as biomarkers of neurological paraneoplastic autoimmunity, research funding from Roche not related to this project and consulting for Alexion Pharmaceuticals without personal compensation; Dr. Tobin reports receiving research funding from the National institutes of Health, Mayo Clinic Center for Multiple Sclerosis and Autoimmune Neurology and Mallinckrodt Inc, he receives royalties from the publication of “Mayo Clinic Cases in Neuroimmunology” (OUP); Paul Decker, Ronald Go, Jithma Abeykoon, Gaurav Goyal, Jason Young, Matthew Koster, Robert Vassallo, Jay Ryu, Caroline Davidge-Pitts, Aishwarya Ravindran, Julio Sartori Valinotti, Nora Bennani, Mithun Shah, Corrie Bach, Jeanette Eckel-Passow declare no competing interests.

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

A list of authors and their affiliations appears at the end of the paper.

A full list of members and their affiliations appears in the Supplementary Information.
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References

1. Go RS Jacobsen E Baiocchi R Buhtoiarov I Butler EB Campbell PK Histiocytic neoplasms, version 2.2021, NCCN clinical practice guidelines in oncology J Natl Compr Cancer Netw 2021 19 1277 303 10.6004/jnccn.2021.0053
Go RS, Jacobsen E, Baiocchi R, Buhtoiarov I, Butler EB, Campbell PK, et al. Histiocytic neoplasms, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Cancer Netw. 2021;19:1277–303.10.6004/jnccn.2021.0053
2. Arnaud L Hervier B Néel A Hamidou MA Kahn J-E Wechsler B CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients Blood J Am Soc Hematol 2011 117 2778 82
Arnaud L, Hervier B, Néel A, Hamidou MA, Kahn J-E, Wechsler B, et al. CNS involvement and treatment with interferon-α are independent prognostic factors in Erdheim-Chester disease: a multicenter survival analysis of 53 patients. Blood J Am Soc Hematol. 2011;117:2778–82.
3. Nathoo N Uhm JH Porter AB Hammack J Jaeckle KA Mrugala MM Clinical features and outcomes in primary nervous systemhistiocytic neoplasms Blood Cancer J 2024 14 101 10.1038/s41408-024-01083-x 38902249
Nathoo N, Uhm JH, Porter AB, Hammack J, Jaeckle KA, Mrugala MM, et al. Clinical features and outcomes in primary nervous systemhistiocytic neoplasms. Blood Cancer J. 2024;14:101.38902249 10.1038/s41408-024-01083-x
4. Goyal G Heaney ML Collin M Cohen-Aubart F Vaglio A Durham BH Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era Blood 2020 135 1929 45 10.1182/blood.2019003507 32187362
Goyal G, Heaney ML, Collin M, Cohen-Aubart F, Vaglio A, Durham BH, et al. Erdheim-Chester disease: consensus recommendations for evaluation, diagnosis, and treatment in the molecular era. Blood. 2020;135:1929–45.32187362 10.1182/blood.2019003507
5. Khalil M Teunissen CE Otto M Piehl F Sormani MP Gattringer T Neurofilaments as biomarkers in neurological disorders Nat Rev Neurol 2018 14 577 89 10.1038/s41582-018-0058-z 30171200
Khalil M, Teunissen CE, Otto M, Piehl F, Sormani MP, Gattringer T, et al. Neurofilaments as biomarkers in neurological disorders. Nat Rev Neurol. 2018;14:577–89.30171200 10.1038/s41582-018-0058-z
6. Goyal G Young JR Abeykoon JP Shah MV Bennani NN Sartori-Valinotti JC Impact of a multidisciplinary tumor board on the care of patients with histiocytic disorders: the Histiocytosis Working Group experience oncologist 2022 27 144 8 10.1093/oncolo/oyab031 35641201
Goyal G, Young JR, Abeykoon JP, Shah MV, Bennani NN, Sartori-Valinotti JC, et al. Impact of a multidisciplinary tumor board on the care of patients with histiocytic disorders: the Histiocytosis Working Group experience. oncologist. 2022;27:144–8.35641201 10.1093/oncolo/oyab031
7. Sjölin K Aulin J Wallentin L Eriksson N Held C Kultima K Serum neurofilament light chain in patients with atrial fibrillation J Am Heart Assoc 2022 11 e025910 10.1161/JAHA.122.025910 35861814
Sjölin K, Aulin J, Wallentin L, Eriksson N, Held C, Kultima K, et al. Serum neurofilament light chain in patients with atrial fibrillation. J Am Heart Assoc. 2022;11:e025910.35861814 10.1161/JAHA.122.025910
8. Hay M Ryan L Huentelman M Konhilas J Hoyer-Kimura C Beach TG Serum neurofilament light is elevated in COVID-19 positive adults in the ICU and is associated with co-morbid cardiovascular disease, neurological complications, and acuity of illness Cardiol Cardiovasc Med 2021 5 551 10.26502/fccm.92920221 34708189
Hay M, Ryan L, Huentelman M, Konhilas J, Hoyer-Kimura C, Beach TG, et al. Serum neurofilament light is elevated in COVID-19 positive adults in the ICU and is associated with co-morbid cardiovascular disease, neurological complications, and acuity of illness. Cardiol Cardiovasc Med. 2021;5:551.34708189 10.26502/fccm.92920221
9. van der Plas E Lullmann O Hopkins L Schultz JL Nopoulos PC Harshman LA Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease Pediatr Res 2022 91 1735 40 10.1038/s41390-021-01649-6 34274959
van der Plas E, Lullmann O, Hopkins L, Schultz JL, Nopoulos PC, Harshman LA. Associations between neurofilament light-chain protein, brain structure, and chronic kidney disease. Pediatr Res. 2022;91:1735–40.34274959 10.1038/s41390-021-01649-6
10. Benkert P Meier S Schaedelin S Manouchehrinia A Yaldizli Ö Maceski A Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study Lancet Neurol 2022 21 246 57 10.1016/S1474-4422(22)00009-6 35182510
Benkert P, Meier S, Schaedelin S, Manouchehrinia A, Yaldizli Ö, Maceski A, et al. Serum neurofilament light chain for individual prognostication of disease activity in people with multiple sclerosis: a retrospective modelling and validation study. Lancet Neurol. 2022;21:246–57.35182510 10.1016/S1474-4422(22)00009-6
11. Gauthier A Viel S Perret M Brocard G Casey R Lombard C Comparison of SimoaTM and EllaTM to assess serum neurofilament‐light chain in multiple sclerosis Ann Clin Transl Neurol 2021 8 1141 50 10.1002/acn3.51355 33830650
Gauthier A, Viel S, Perret M, Brocard G, Casey R, Lombard C, et al. Comparison of SimoaTM and EllaTM to assess serum neurofilament‐light chain in multiple sclerosis. Ann Clin Transl Neurol. 2021;8:1141–50.33830650 10.1002/acn3.51355
12. Gavhed D Åkefeldt SO Österlundh G Laurencikas E Hjorth L Blennow K Biomarkers in the cerebrospinal fluid and neurodegeneration in Langerhans cell histiocytosis Pediatr Blood Cancer 2009 53 1264 70 10.1002/pbc.22238 19688833
Gavhed D, Åkefeldt SO, Österlundh G, Laurencikas E, Hjorth L, Blennow K, et al. Biomarkers in the cerebrospinal fluid and neurodegeneration in Langerhans cell histiocytosis. Pediatr Blood Cancer 2009;53:1264–70.19688833 10.1002/pbc.22238
13. Sveijer M von Bahr Greenwood T Jädersten M Kvedaraite E Zetterberg H Blennow K Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma Br J Haematol 2022 198 721 8 10.1111/bjh.18247 35582775
Sveijer M, von Bahr Greenwood T, Jädersten M, Kvedaraite E, Zetterberg H, Blennow K, et al. Screening for neurodegeneration in Langerhans cell histiocytosis with neurofilament light in plasma. Br J Haematol. 2022;198:721–8.35582775 10.1111/bjh.18247
14. Henter JI Kvedaraite E Martín Muñoz D Cheng Munthe‐Kaas M Zeller B Nystad TA Response to mitogen‐activated protein kinase inhibition of neurodegeneration in Langerhans cell histiocytosis monitored by cerebrospinal fluid neurofilament light as a biomarker: a pilot study Br J Haematol 2022 196 248 54 10.1111/bjh.17781 34435355
Henter JI, Kvedaraite E, Martín Muñoz D, Cheng Munthe‐Kaas M, Zeller B, Nystad TA, et al. Response to mitogen‐activated protein kinase inhibition of neurodegeneration in Langerhans cell histiocytosis monitored by cerebrospinal fluid neurofilament light as a biomarker: a pilot study. Br J Haematol. 2022;196:248–54.34435355 10.1111/bjh.17781
