Giulio Disanto1, Rocco Adiutori2, Ruth Dobson2, Vittorio Martinelli3, Gloria Dalla Costa3, Tessel Runia4, Evgeniy Evdoshenko5, Eric Thouvenot6, Maria Trojano7, Niklas Norgren8, Charlotte Teunissen9, Ludwig Kappos10, Gavin Giovannoni2, Jens Kuhle11. 1. Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK Neurocentre of Southern Switzerland, Ospedale Civico, Lugano, Switzerland. 2. Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK. 3. Department of Neurology and INSPE, Vita-Salute San Raffaele University, Scientific Institute San Raffaele, Milan, Italy. 4. Department of Neurology, Erasmus MC University Medical Center, Rotterdam, The Netherlands. 5. Centre of Multiple Sclerosis, City Clinical Hospital 31, St. Petersburg, Russia. 6. Institut de Génomique Fonctionnelle, CNRS UMR5203, INSERM U661, Université Montpellier 1, Université Montpellier 2, Montpellier, France, and Université Montpellier and Hôpital Carémeau, Nîmes, France. 7. Department of Basic Medical Sciences, Neuroscience and Sense Organs, University of Bari, Bari, Italy. 8. Uman Diagnostics, Umeå, Sweden. 9. Neurochemistry Laboratory and Biobank, Department of Clinical Chemistry, MS Center, Neurocampus Amsterdam, VU University Medical Centre Amsterdam, The Netherlands. 10. Department of Neurology, University Hospital Basel, Basel, Switzerland. 11. Queen Mary University of London, Blizard Institute, Barts and The London School of Medicine and Dentistry, London, UK Department of Neurology, University Hospital Basel, Basel, Switzerland.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
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