Leavitt Victoria, Mostert Jop, Comtois Jacynthe, Moral Ester, Brieva Luis, Repovic Pavle, Bowen James D, Uitdehaag Bernard, Strijbis Eva, Cutter Gary, Koch Marcus W
Department of Neurology, Columbia University Irving Medical Center, New York, USA.
Department of Neurology, Rijnstate Hospital, Arnhem, The Netherlands.
J Neurol. 2025 Apr 12;272(5):338. doi: 10.1007/s00415-025-13066-4.
Cognitive impairment is common in multiple sclerosis (MS). Accurate measurement of cognitive change is essential for clinical trials.
The change in cognitive scores, clinical metrics of physical disability, and neuroradiological metrics was quantified in data from a phase-3 randomized controlled trial of natalizumab in secondary progressive MS (SPMS). The adults diagnosed with SPMS for ≥ 2 years and Expanded Disability Status Scale (EDSS) scores from 3 to 6.5 were randomized to receive natalizumab or placebo for 96 weeks. We evaluated change in Symbol Digit Modalities Test (SDMT), Paced Auditory Serial Addition Test (PASAT), Selective Reminding Test (SRT), Brief Visuospatial Memory Test (BVMT-R), two subjective cognitive measures, Beck Depression Inventory (BDI-FS), Timed 25-foot Walk Test, Nine Hole Peg Test, measures of brain volume, and T2 lesion volume.
The outcomes were evaluated at baseline, 48-, and 96-week follow-up. There were no significant differences in cognitive change between treatment arms. SDMT and PASAT scores improved over 96-weeks: mean SDMT scores by 4.5 points (SD 9.3), mean PASAT scores by 2.4 points (SD 9.4). Verbal and visuospatial memory test performance showed no consistent change. All MRI measures showed decreased brain volumes. NHPT scores worsened little and T25FW showed steadily worsening scores.
Improvements in SDMT and PASAT performance were observed regardless of treatment arm. These findings are consistent with prior studies in MS. As it is unlikely that cognition improves over time in people with a chronic neurologic disease, these results support the need for cognitive outcomes that overcome practice and learning effects to accurately quantify change.
认知障碍在多发性硬化症（MS）中很常见。准确测量认知变化对于临床试验至关重要。
在一项那他珠单抗治疗继发进展型MS（SPMS）的3期随机对照试验的数据中，对认知评分、身体残疾的临床指标和神经放射学指标的变化进行了量化。将诊断为SPMS≥2年且扩展残疾状态量表（EDSS）评分在3至6.5之间的成年人随机分为接受那他珠单抗或安慰剂治疗96周。我们评估了符号数字模态测验（SDMT）、听觉连续加法测验（PASAT）、选择性提醒测验（SRT）、简短视觉空间记忆测验（BVMT-R）、两项主观认知测量、贝克抑郁量表（BDI-FS）、25英尺定时步行试验、九孔插板试验、脑容量测量和T2病变体积的变化。
在基线、48周和96周随访时评估结果。治疗组之间在认知变化方面没有显著差异。SDMT和PASAT评分在96周内有所改善：SDMT平均评分提高4.5分（标准差9.3），PASAT平均评分提高2.4分（标准差9.4）。言语和视觉空间记忆测试表现没有一致的变化。所有MRI测量均显示脑容量减少。NHPT评分略有恶化，T25FW评分稳步恶化。
无论治疗组如何，均观察到SDMT和PASAT表现有所改善。这些发现与先前MS研究一致。由于慢性神经疾病患者的认知不太可能随时间改善，这些结果支持需要克服练习和学习效应的认知结果来准确量化变化。
