Zurawski Jonathan, Tauhid Shahamat, Healy Brian C, Chu Renxin, Houtchens Maria K, Jalkh Youmna, Khalil Samar, Quattrucci Molly, Mateen Farrah J, Napoli Salvatore, Rizvi Syed, Singhal Tarun, Bakshi Rohit
Departments of Neurology, Brigham & Women's Hospital Multiple Sclerosis Center, Ann Romney Center for Neurological Diseases, Laboratory for Neuroimaging Research, Harvard Medical School, Boston, Massachusetts, USA.
Departments of Biostatistics, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
J Neuroimaging. 2025 Mar-Apr;35(2):e70032. doi: 10.1111/jon.70032.
Cladribine, an FDA-approved disease-modifying immunotherapy for multiple sclerosis (MS), penetrates the CSF and mitigates T cells and B cells, and thus may impact the development of cortical gray matter lesions (CLs) and leptomeningeal enhancement (LME). 7T MRI is a highly sensitive tool for monitoring these outcomes in relapsing-remitting (RR) MS.
MS subjects (n = 19, age [mean ± standard deviation]: 48.8 ± 10.0 years, 63.1% RRMS, 36.9% secondary progressive MS, Expanded Disability Status Scale [EDSS] score 4.1 ± 2.0) underwent 7T MRI with 0.7-mm voxels within a mean 1.9 months of oral cladribine initiation and ∼1 year later in this real-world study. CLs and LME were quantified by an expert. Wilcoxon signed rank tests and paired t-tests compared baseline to follow-up data.
A total of 88.2% of subjects had CLs at baseline (mean 14.1 CLs/patient, range 1-77). No subjects accrued new CLs, and CL volume remained stable (0.33 ± 0.48 mL baseline vs. 0.31 ± 0.46 mL follow-up, p = 0.22). LME was found in 88.9% of subjects at baseline. LME foci number was stable in seven (41.2%), increased in five (29.4%), and decreased in five (29.4%) subjects at follow-up, but overall LME burden was stable (3.1 ± 1.8 vs. 3.2 ± 1.6 foci per subject, p = 1.0). No EDSS or timed 25-foot walk change was noted (both p > 0.35). No subjects had clinical relapses or new T2 or gadolinium-enhancing white matter lesions during the study.
These observational data suggest that cladribine therapy stabilizes cortical demyelination in MS over the first year of treatment. Overall, LME burden remained stable over 1 year; however, within-subject resolution and accrual were noted.
克拉屈滨是一种经美国食品药品监督管理局（FDA）批准用于治疗多发性硬化症（MS）的疾病修正免疫疗法，它可穿透脑脊液并减轻T细胞和B细胞，因此可能会影响皮质灰质病变（CLs）和软脑膜强化（LME）的发展。7T磁共振成像（MRI）是监测复发缓解型（RR）MS这些结果的高度敏感工具。
在这项真实世界研究中，MS受试者（n = 19，年龄[平均值±标准差]：48.8±10.0岁，63.1%为RRMS，36.9%为继发进展型MS，扩展残疾状态量表[EDSS]评分4.1±2.0）在开始口服克拉屈滨后平均1.9个月内及约1年后接受了体素为0.7毫米的7T MRI检查。CLs和LME由一名专家进行量化。采用Wilcoxon符号秩检验和配对t检验比较基线数据与随访数据。
共有88.2%的受试者在基线时存在CLs（平均每位患者14.1个CLs，范围为1 - 77个）。没有受试者出现新的CLs，且CL体积保持稳定（基线时为0.33±0.48毫升，随访时为0.31±0.46毫升，p = 0.22）。88.9%的受试者在基线时发现有LME。随访时，7名受试者（41.2%）的LME病灶数量稳定，5名受试者（29.4%）增加，5名受试者（29.4%）减少，但总体LME负担保持稳定（每位受试者分别为3.1±1.8个病灶和3.2±1.6个病灶，p = 1.0）。未观察到EDSS或25英尺步行时间的变化（两者p均>0.35）。在研究期间，没有受试者出现临床复发或新的T2或钆增强白质病变。
这些观察数据表明，在治疗的第一年，克拉屈滨疗法可使MS患者的皮质脱髓鞘稳定。总体而言，LME负担在1年内保持稳定；然而，个体内部的消退和出现情况也被注意到。
