Sacco Simone, Papinutto Nico, Schoeps Vinicius A, Cheng Shuiting, Stern William A, Zhao Haojun, Bischof Antje, Caverzasi Eduardo, Dombagahawatta Manula, Juwono Jeremy, Akula Amit, Cordano Christian, Beaudry-Richard Alexandra, Gomez Refujia, Harms Meagan, Santaniello Adam, Bove Riley M, Gelfand Jeffrey M, Goodin Douglas S, Green Ari J, Oksenberg Jorge R, Waubant Emmanuelle, Wilson Michael R, Zamvil Scott S, Cree Bruce A C, Hauser Stephen L, Henry Roland G
Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA, USA.
Department of Neurology, University Hospital of Muenster, Muenster, Germany.
Ann Neurol. 2025 Jun 24. doi: 10.1002/ana.27298.
Spinal cord (SC) atrophy correlates with and predicts the underlying progressive biology in active and non-active multiple sclerosis (MS), thereby providing a biomarker for clinical trials and patient management. Initiation of disease-modifying therapy (DMT) may be followed by early pronounced central nervous system (CNS) volume loss due to resolution of inflammation (pseudoatrophy) and confounding the interpretation of atrophy. High-dose glucocorticoids (HDGs) reduce inflammation and might therefore modify pseudoatrophy.
One hundred twenty-three newly diagnosed and DMT-naïve MS participants (relapsing-remitting, 70% female participants, median age = 36 years, Expanded Disability Status Scale [EDSS] 2.0) were followed for up to 3 years. Forty-two participants received HDG before baseline magnetic resonance imaging (MRI; DMT-HDG; median = 52 days, interquartile range [IQR] = 37-71), whereas 60 did not (DMT/no-HDG). Twenty-one participants remained untreated (no-DMT), and 102 started DMT after baseline MRI. SC total cervical cord cross-sectional area (TCA), gray matter area (GMA), and white matter area (WMA) and regional brain volumes were analyzed using mixed effects models.
The DMT-HDG, DMT/no-HDG, and no-DMT groups had similar demographic, clinical, and radiological features. Pronounced SC pseudoatrophy was observed based on more year 1 versus year 2 volume loss for DMT/no-HDG (-2.06% vs. 0.83%; P = 0.02) but not DMT-HDG (-0.51% vs. 0.66%; P = 0.8) and more year 1 volume loss for DMT/no-HDG compared to DMT-HDG (-2.06% vs. 0.51%; P = 0.02).
HDG preceding baseline MRI suppresses CNS white matter (WM) pseudoatrophy after DMT initiation, most conspicuously for the SC. Suppression of pseudoatrophy with HDG may improve the fidelity of clinical trials and enhance the feasibility for short-term trials with SC and brain MRI outcomes in active MS by pretreatment with HDG. ANN NEUROL 2025.
脊髓萎缩与活动性和非活动性多发性硬化症（MS）的潜在进展生物学相关并可预测其发展，从而为临床试验和患者管理提供一种生物标志物。开始疾病修饰治疗（DMT）后，由于炎症消退（假性萎缩），可能会出现早期明显的中枢神经系统（CNS）体积减少，这会混淆对萎缩的解读。高剂量糖皮质激素（HDG）可减轻炎症，因此可能会改变假性萎缩。
对123名新诊断且未接受过DMT治疗的MS参与者（复发缓解型，70%为女性参与者，中位年龄 = 36岁，扩展残疾状态量表[EDSS]为2.0）进行了长达3年的随访。42名参与者在基线磁共振成像（MRI）前接受了HDG治疗（DMT-HDG组；中位时间 = 52天，四分位间距[IQR] = 37 - 71），而60名未接受（DMT/无HDG组）。21名参与者未接受治疗（无DMT组），102名在基线MRI后开始DMT治疗。使用混合效应模型分析脊髓颈段总横截面积（TCA）、灰质面积（GMA）、白质面积（WMA）和脑区体积。
DMT-HDG组、DMT/无HDG组和无DMT组在人口统计学、临床和放射学特征方面相似。基于DMT/无HDG组第1年与第2年的体积减少情况（-2.06%对0.83%；P = 0.02），观察到明显的脊髓假性萎缩，但DMT-HDG组未观察到（-0.51%对0.66%；P = 0.8），且DMT/无HDG组第1年的体积减少比DMT-HDG组更多（-2.06%对0.51%；P = 0.02）。
基线MRI前使用HDG可抑制DMT开始后CNS白质（WM）假性萎缩，对脊髓最为明显。HDG抑制假性萎缩可能会提高临床试验的准确性，并通过HDG预处理增强在活动性MS中以脊髓和脑MRI结果为指标的短期试验的可行性。《神经病学纪事》2025年。
