Stork Lidia, Haupts Michael, Kruse Niels, Spill-Askeridis Petra, Kutllovci Adriane, Weber Martin S, Brück Wolfgang, Metz Imke
Institute of Neuropathology, University Medical Center Göttingen, Germany.
Department of Neurology, University Hospital Düsseldorf, Germany.
Free Neuropathol. 2023 Oct 5;4:15. doi: 10.17879/freeneuropathology-2023-5049. eCollection 2023 Jan.
In progressive multiple sclerosis (MS) patients, CNS inflammation trapped behind a closed blood brain barrier drives continuous neuroaxonal degeneration, thus leading to deterioration of neurological function. Therapeutics in progressive MS are limited. High-dose intravenous glucocorticosteroids (HDCS) can cross the blood-brain barrier and may reduce inflammation within the CNS. However, the treatment efficacy of HDCS in progressive MS remains controversial. Serum neurofilament light chains (sNfL) are an established biomarker of neuroaxonal degeneration and are used to monitor treatment responses. We aimed to investigate whether repeated cycles of intravenous HDCS reduce the level of sNfL in progressive MS patients. We performed a monocentric observational study of 25 patients recruited during ongoing clinical routine care who were treated with repeated cycles of intravenous HDCS as long-term therapy for their progressive MS. sNfL were measured in 103 repeated blood samples (median time interval from baseline 28 weeks, range 2-55 weeks) with the Single Molecular Array (SiMoA) technology. The Expanded Disability Status Score (EDSS) was documented at baseline and follow-up. The median age of patients was 55 years (range 46-77 years) with a median disease duration of 26 years (range 11-42 years). sNfL baseline levels at study inclusion were significantly higher in progressive MS patients compared to age-matched healthy controls (median 16.7 pg/ml vs 11.5 pg/ml, p=0.002). sNfL levels showed a positive correlation with patient age (r=0.2, p=0.003). The majority of patients (72%, 16/23) showed reduced sNfL levels ≥20 weeks after HDCS compared to baseline (median 13.3 pg/ml, p=0.03). sNfL levels correlated negatively with the time interval from baseline HDCS therapy (r=-0.2, p=0.03). This association was also evident after correction for treatment with disease-modifying drugs (adjusted R=0.10, p=0.001). The EDSS remained stable (median 6.5) within a median treatment duration of 26 weeks (range 13-51 weeks). Although larger studies are needed to confirm our findings, we were able to demonstrate that HDCS treatment reduces sNfL levels and therefore may slow down neuroaxonal damage in a subgroup of patients with progressive MS. Moreover, a stable EDSS was observed during therapy. Findings suggest that HDCS may be beneficial for the treatment of progressive MS.
在进展性多发性硬化症（MS）患者中，被困在封闭血脑屏障后的中枢神经系统炎症驱动神经轴突持续退化，从而导致神经功能恶化。进展性MS的治疗方法有限。大剂量静脉注射糖皮质激素（HDCS）可以穿过血脑屏障，并可能减轻中枢神经系统内的炎症。然而，HDCS在进展性MS中的治疗效果仍存在争议。血清神经丝轻链（sNfL）是已确立的神经轴突退化生物标志物，用于监测治疗反应。我们旨在研究静脉注射HDCS的重复疗程是否能降低进展性MS患者的sNfL水平。我们对25例在正在进行的临床常规护理中招募的患者进行了一项单中心观察性研究，这些患者接受静脉注射HDCS的重复疗程作为其进展性MS的长期治疗。使用单分子阵列（SiMoA）技术在103份重复血液样本中测量sNfL（从基线起的中位时间间隔为28周，范围为2 - 55周）。在基线和随访时记录扩展残疾状态评分（EDSS）。患者的中位年龄为55岁（范围46 - 77岁），中位病程为26年（范围11 - 42年）。与年龄匹配的健康对照相比，进展性MS患者在研究纳入时的sNfL基线水平显著更高（中位值16.7 pg/ml对11.5 pg/ml，p = 0.002）。sNfL水平与患者年龄呈正相关（r = 0.2，p = 0.003）。与基线相比，大多数患者（72%，16/23）在HDCS治疗≥20周后sNfL水平降低（中位值13.3 pg/ml，p = 0.03）。sNfL水平与从基线HDCS治疗开始的时间间隔呈负相关（r = -0.2，p = 0.03）。在对疾病修饰药物治疗进行校正后，这种关联也很明显（调整后的R = 0.10，p = 0.001）。在中位治疗持续时间26周（范围13 - 51周）内，EDSS保持稳定（中位值6.5）。尽管需要更大规模的研究来证实我们的发现，但我们能够证明HDCS治疗可降低sNfL水平，因此可能减缓一部分进展性MS患者的神经轴突损伤。此外，在治疗期间观察到EDSS稳定。研究结果表明，HDCS可能对进展性MS的治疗有益。
