Novakova Lenka, Zetterberg Henrik, Sundström Peter, Axelsson Markus, Khademi Mohsen, Gunnarsson Martin, Malmeström Clas, Svenningsson Anders, Olsson Tomas, Piehl Fredrik, Blennow Kaj, Lycke Jan
From the Department of Clinical Neuroscience (L.N., M.A., C.M., J.L.) and Department of Psychiatry and Neurochemistry (H.Z., K.B.), Institute of Neuroscience and Physiology at Sahlgrenska Academy, University of Gothenburg; Clinical Neurochemistry Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Mölndal, Sweden; Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, London, UK; Department of Pharmacology and Clinical Neuroscience (P.S.), Umeå University; University Department of Clinical Neuroscience (M.K., T.O., F.P.), Neuroimmunology Unit, and Department of Clinical Sciences (A.S.), Danderyd Hospital, Karolinska Institutet, Stockholm; and Department of Neurology (M.G.), Faculty of Medicine and Health, Örebro University, Sweden.
Neurology. 2017 Nov 28;89(22):2230-2237. doi: 10.1212/WNL.0000000000004683. Epub 2017 Oct 27.
To examine the effects of disease activity, disability, and disease-modifying therapies (DMTs) on serum neurofilament light (NFL) and the correlation between NFL concentrations in serum and CSF in multiple sclerosis (MS).
NFL concentrations were measured in paired serum and CSF samples (n = 521) from 373 participants: 286 had MS, 45 had other neurologic conditions, and 42 were healthy controls (HCs). In 138 patients with MS, the serum and CSF samples were obtained before and after DMT treatment with a median interval of 12 months. The CSF NFL concentration was measured with the UmanDiagnostics NF-light enzyme-linked immunosorbent assay. The serum NFL concentration was measured with an in-house ultrasensitive single-molecule array assay.
In MS, the correlation between serum and CSF NFL was = 0.62 ( < 0.001). Serum concentrations were significantly higher in patients with relapsing-remitting MS (16.9 ng/L) and in patients with progressive MS (23 ng/L) than in HCs (10.5 ng/L, < 0.001 and < 0.001, respectively). Treatment with DMT reduced median serum NFL levels from 18.6 (interquartile range [IQR] 12.6-32.7) ng/L to 15.7 (IQR 9.6-22.7) ng/L ( < 0.001). Patients with relapse or with radiologic activity had significantly higher serum NFL levels than those in remission ( < 0.001) or those without new lesions on MRI ( < 0.001).
Serum and CSF NFL levels were highly correlated, indicating that blood sampling can replace CSF taps for this particular marker. Disease activity and DMT had similar effects on serum and CSF NFL concentrations. Repeated NFL determinations in peripheral blood for detecting axonal damage may represent new possibilities in MS monitoring.
研究疾病活动度、残疾程度和疾病修正治疗（DMTs）对血清神经丝轻链（NFL）的影响，以及多发性硬化症（MS）患者血清和脑脊液中NFL浓度之间的相关性。
对373名参与者的配对血清和脑脊液样本（n = 521）进行NFL浓度测量：286例患有MS，45例患有其他神经系统疾病，42例为健康对照（HCs）。在138例MS患者中，于DMT治疗前后采集血清和脑脊液样本，中位间隔时间为12个月。采用UmanDiagnostics NF-light酶联免疫吸附测定法测量脑脊液NFL浓度。采用内部超灵敏单分子阵列测定法测量血清NFL浓度。
在MS患者中，血清和脑脊液NFL之间的相关性为 = 0.62（< 0.001）。复发缓解型MS患者（16.9 ng/L）和进展型MS患者（23 ng/L）的血清浓度显著高于HCs（10.5 ng/L，分别为< 0.001和< 0.001）。DMT治疗使血清NFL中位数水平从18.6（四分位间距[IQR] 12.6 - 32.7）ng/L降至15.7（IQR 9.6 - 22.7）ng/L（< 0.001）。复发或有影像学活动的患者血清NFL水平显著高于缓解期患者（< 0.001）或MRI上无新病灶的患者（< 0.001）。
血清和脑脊液NFL水平高度相关，表明对于这一特定标志物，采血可替代脑脊液穿刺。疾病活动度和DMT对血清和脑脊液NFL浓度有相似影响。通过反复检测外周血中的NFL来检测轴突损伤可能为MS监测带来新的可能性。
