Spinal Cord Injury Center, University Hospital Balgrist, Zurich, Switzerland.
Department of Neurology, University Hospital and University of Zurich, Zurich, Switzerland.
Mult Scler Relat Disord. 2022 Jul;63:103802. doi: 10.1016/j.msard.2022.103802. Epub 2022 Apr 10.
Walking impairment is a common and highly disabling symptom in people with MS (PwMS). Ambulatory deterioration is poorly characterized in PwMS and reliable prognosis that may guide clinical decisions is elusive. This study aimed to objectively track the progression of clinical walking performance and kinematic gait patterns in PwMS over 4 years, thereby revealing potential prognostic markers for deterioration of ambulatory function.
Twenty-two PwMS (48.8 ± 9.9 years, 14 females; expanded disability status scale [EDSS]: 4.5 ± 0.9 points) with gait impairments were recruited at the University Hospital Zurich, Switzerland. Gait function was monitored over a period of 4 years using a set of standardized clinical walking tests (timed 25-foot walk [T25FW], 6 min walk test [6MWT], 12-item MS walking scale [MSWS-12]) and comprehensive 3D kinematic gait analysis. Walking decline was assessed in the full patient cohort and in patient sub-groups that were built according to MS type (relapsing-remitting [RRMS], progressive [PMS]) and subjects' pathological gait signature (cluster groups 1-3).
In the total cohort (n = 22), we found a significant worsening in the 6MWT (BL vs. 4y: -41.1 m; P = 0.0053), while the performance in the T25FW, MSWS-12 and the EDSS remained unchanged over 4 years. Subjects with PMS (n = 12) showed a significant worsening in the EDSS (BL vs. 4y: +0.6 points; P = 0.0053), which was not observed in participants with RRMS (n = 10). Whereas deterioration of clinical walking function was not different between subjects with RRMS and PMS, we identified differences in clinical walking deterioration between PwMS with varying gait pattern pathologies: Subjects with spastic-paretic gait impairments (cluster 1; n = 9) demonstrated a marked worsening in the T25FW (BL vs. 4y: +2 s; P = 0.0020) and 6MWT (BL vs. 4y: -92.9 m; P < 0.0001) which was not seen in PwMS with an ataxia-like (cluster 2; n = 8) or unstable walking pattern (cluster 3; n = 5). Deterioration of clinical walking performance in cluster 1 was accompanied by a specific worsening of gait deficits that were characteristic of this cluster at baseline, a phenomenon not found in the other sub-groups. Accordingly, aggravation of cluster 1-specific gait impairments over 4 years predicted deterioration of the 6MWT in the total cohort (n = 22) with an accuracy of 90.9% (sensitivity: 90.9%; specificity: 90.9%; Nagelkerkes coefficient of determination R2: 0.721), unveiling key determinants of MS-related walking decline.
Our findings highlight the potential of quantitative, functional outcomes for objective tracking of disease progression in PwMS. Gait pattern analysis can provide valuable information on the underlying pathomechanisms of gait deterioration and may represent a complementary prognostic tool for walking function in PwMS.
clinicaltrials.gov, NCT01576354.
行走障碍是多发性硬化症患者（PwMS）常见且高度致残的症状。PwMS 的步行能力恶化情况描述不足，难以可靠地预测可能指导临床决策的预后。本研究旨在客观地跟踪 PwMS 在 4 年内的临床行走表现和运动步态模式的进展，从而揭示与步行功能恶化相关的潜在预后标志物。
22 名有步态障碍的 PwMS（48.8±9.9 岁，14 名女性；扩展残疾状态量表 [EDSS]：4.5±0.9 分）在瑞士苏黎世大学医院被招募。使用一系列标准化的临床行走测试（定时 25 英尺行走 [T25FW]、6 分钟步行测试 [6MWT]、12 项多发性硬化症行走量表 [MSWS-12]）和全面的 3D 运动步态分析，在 4 年内监测步态功能。在整个患者队列和根据 MS 类型（复发缓解型 [RRMS]、进行性 [PMS]）和患者病理步态特征（聚类组 1-3）构建的患者亚组中评估行走下降情况。
在总队列（n=22）中，我们发现 6MWT 明显恶化（BL 与 4y：-41.1m；P=0.0053），而 T25FW、MSWS-12 和 EDSS 的表现在 4 年内保持不变。PMS 患者（n=12）的 EDSS 明显恶化（BL 与 4y：+0.6 分；P=0.0053），而 RRMS 患者（n=10）未观察到这种情况。尽管 RRMS 和 PMS 患者的临床行走功能恶化无差异，但我们发现不同步态病理患者的临床行走恶化存在差异：痉挛性偏瘫步态障碍患者（聚类 1；n=9）的 T25FW（BL 与 4y：+2s；P=0.0020）和 6MWT（BL 与 4y：-92.9m；P<0.0001）明显恶化，而共济失调样步态障碍患者（聚类 2；n=8）或不稳定步态障碍患者（聚类 3；n=5）则没有。聚类 1 患者的临床行走能力恶化伴随着基线时该聚类特征的步态缺陷的特定恶化，而在其他亚组中未发现这种现象。因此，聚类 1 特异性步态障碍恶化超过 4 年可以预测总队列（n=22）的 6MWT 恶化，准确率为 90.9%（灵敏度：90.9%；特异性：90.9%；Nagelkerke 决定系数 R2：0.721），揭示了 MS 相关行走下降的关键决定因素。
我们的研究结果强调了定量、功能结果在 PwMS 疾病进展客观跟踪中的潜力。步态模式分析可以为步态恶化的潜在病理机制提供有价值的信息，并可能成为 PwMS 行走功能的补充预后工具。
clinicaltrials.gov，NCT01576354。
