Temporal Dynamics of Plasma Neurofilament Light in Blood Donors With Preclinical Multiple Sclerosis.

IF 7.8 1区 医学 Q1 CLINICAL NEUROLOGY Neurology® Neuroimmunology & Neuroinflammation Pub Date : 2025-01-01 Epub Date: 2024-11-27 DOI:10.1212/NXI.0000000000200335
Josefine Britze, Margit Hørup Larsen, Anders Gorm Pedersen, Susanne Rosthøj, Helle Bach Søndergaard, Melinda Magyari, Ole Birger Pedersen, Bitten Aagaard Jensen, Sisse Rye Ostrowski, Christian Erikstrup, Henrik Ullum, Jette Lautrup Frederiksen Battistini, Finn Sellebjerg, Signe Modvig
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Abstract

Background and objectives: Multiple sclerosis (MS) is a CNS disease, characterized by demyelination, inflammation, and neurodegeneration. Recent advances in technology allow measurement of the axonal damage marker neurofilament light chain in peripheral blood. Two studies have shown that patients with MS have elevated neurofilament light levels before their first symptom, but longitudinal studies are lacking. We aimed to investigate the intraindividual neurofilament light dynamics during the presymptomatic phase of MS.

Methods: The Danish Blood Donor Study (DBDS) has stored plasma samples from blood donors for more than 10 years. We identified DBDS participants, who had subsequently been diagnosed with MS, and included all samples donated before their first demyelinating symptom (median 5.00 samples per case). As controls, we included 2 healthy donors per case. Plasma levels of neurofilament light were measured and compared with quality-of-life data. We used a Bayesian approach to derive estimates for the percentage of cases with presymptomatic increased neurofilament light levels.

Results: We observed that 12 (17%, 95% CI 9%-28%) of 69 presymptomatic MS donors had intermittently increased neurofilament light levels preclinically. Increased levels were present up to 9 years before clinical onset, also in primary progressive MS. Healthy donors and presymptomatic MS donors with and without increased neurofilament light levels reported equally high physical and mental well-being. Model-based estimates suggested that 55% of cases (95% credible interval [28%-87%]) had experienced increased presymptomatic neurofilament light levels.

Discussion: Patients with MS periodically sustain axonal injury up to 9 years before clinical onset, even in primary progressive disease. This most likely represents asymptomatic disease activity. Some or even all patients are affected by this intermittent axonal injury, prompting the need for further studies of the presymptomatic phase in relation to prognosis and as a therapeutic window of opportunity.

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临床前多发性硬化症献血者血浆神经丝光的时间动态变化
背景和目的:多发性硬化症(MS)是一种中枢神经系统疾病,以脱髓鞘、炎症和神经变性为特征。近年来,随着技术的进步,可以测量外周血中轴突损伤标志物神经丝轻链。两项研究表明,多发性硬化症患者在首次出现症状前神经丝蛋白轻链水平就已升高,但缺乏纵向研究。我们的目的是调查多发性硬化症症状前阶段个体内部神经丝蛋白光的动态变化:方法:丹麦献血者研究(DBDS)已将献血者的血浆样本保存了 10 多年。我们确定了后来被诊断为多发性硬化症的 DBDS 参与者,并纳入了他们首次出现脱髓鞘症状之前捐献的所有样本(每个病例的样本中位数为 5.00)。作为对照,我们为每个病例纳入了 2 名健康捐献者。我们测量了血浆中神经丝光的水平,并将其与生活质量数据进行了比较。我们使用贝叶斯方法估算了症状前神经丝光水平升高病例的百分比:我们观察到,在 69 名无症状多发性硬化症供体中,有 12 人(17%,95% CI 9%-28%)在临床前出现间歇性神经丝光水平增高。在原发性进行性多发性硬化症中,神经丝光水平增高也出现在临床发病前9年。健康捐献者和有或没有神经丝光水平增高的症状前多发性硬化症捐献者都报告了同样高的身心健康水平。基于模型的估算表明,55%的病例(95%可信区间[28%-87%])在症状前神经丝光水平有所增高:讨论:多发性硬化症患者在临床发病前9年内会周期性地受到轴突损伤,即使是原发性进行性疾病患者也不例外。这很可能是无症状的疾病活动。部分甚至所有患者都会受到这种间歇性轴索损伤的影响,因此有必要进一步研究无症状期与预后的关系,并将其作为治疗的机会之窗。
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来源期刊
CiteScore
15.60
自引率
2.30%
发文量
219
审稿时长
8 weeks
期刊介绍: Neurology Neuroimmunology & Neuroinflammation is an official journal of the American Academy of Neurology. Neurology: Neuroimmunology & Neuroinflammation will be the premier peer-reviewed journal in neuroimmunology and neuroinflammation. This journal publishes rigorously peer-reviewed open-access reports of original research and in-depth reviews of topics in neuroimmunology & neuroinflammation, affecting the full range of neurologic diseases including (but not limited to) Alzheimer's disease, Parkinson's disease, ALS, tauopathy, and stroke; multiple sclerosis and NMO; inflammatory peripheral nerve and muscle disease, Guillain-Barré and myasthenia gravis; nervous system infection; paraneoplastic syndromes, noninfectious encephalitides and other antibody-mediated disorders; and psychiatric and neurodevelopmental disorders. Clinical trials, instructive case reports, and small case series will also be featured.
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