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Research paper
Serum neurofilament light chain levels are increased in patients with a clinically isolated syndrome
  1. Giulio Disanto1,2,
  2. Rocco Adiutori1,
  3. Ruth Dobson1,
  4. Vittorio Martinelli3,
  5. Gloria Dalla Costa3,
  6. Tessel Runia4,
  7. Evgeniy Evdoshenko5,
  8. Eric Thouvenot6,
  9. Maria Trojano7,
  10. Niklas Norgren8,
  11. Charlotte Teunissen9,
  12. Ludwig Kappos10,
  13. Gavin Giovannoni1,
  14. Jens Kuhle1,10
  15. on behalf of the International Clinically Isolated Syndrome Study Group
  1. 1Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK
  2. 2Neurocentre of Southern Switzerland, Ospedale Civico, Lugano, Switzerland
  3. 3Department of Neurology and INSPE, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy
  4. 4Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands
  5. 5Centre of Multiple Sclerosis, City Clinical Hospital 31, St. Petersburg, Russia
  6. 6Institut de Génomique Fonctionnelle, CNRS UMR5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, Montpellier, France, and Université Montpellier and Hôpital Carémeau, Nîmes, France
  7. 7Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy
  8. 8Uman Diagnostics, Umeå, Sweden
  9. 9Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, MS Center, Neurocampus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands
  10. 10Department of Neurology, University Hospital Basel, Basel, Switzerland
  1. Correspondence to Dr Jens Kuhle, Neurology, University Hospital Basel, Petersgraben 4, Basel 4031, Switzerland; jens.kuhle{at}


Background Neurofilament light chain (NfL) represents a promising biomarker for axonal injury. We present the first exploratory study on serum NfL in patients with a clinically isolated syndrome (CIS) and healthy controls.

Methods We investigated serum NfL levels in 100 patients with CIS with a short conversion interval to clinically definite multiple sclerosis (MS) (fast converters (FC), median (IQR) conversion time: 110 days (79–139)); 98 patients with non-converting CIS (non-converters (NC), follow-up: 6.5 years (5.3–7.9)); and 92 healthy controls.

Results NfL levels were higher in FC (24.1 pg/mL (13.5–51.8)) and NC (19.3 pg/mL (13.6–35.2)) than in healthy controls (7.9 pg/mL (5.6–17.2)) (OR=5.85; 95% CI 2.63 to 13.02; p=1.5×10−5 and OR=7.03; 95% CI 2.85 to 17.34; p=2.3×10−5, respectively). When grouping FC and NC, increased serum NfL concentration was also associated with increasing numbers of T2 hyperintense MRI lesions (OR=2.36; 95% CI 1.21 to 4.59; p=0.011), gadolinium-enhancing lesions (OR=2.69; 95% CI 1.13 to 6.41; p=0.026) and higher disability scores (OR=2.54; 95% CI 1.21 to 5.31; p=0.013) at CIS diagnosis.

Conclusions If replicated in future studies, serum NfL may represent a reliable and easily accessible biomarker of early axonal damage in CIS and MS.


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