目的:这项针对多发性硬化症(MS)伴步行残疾的参与者的干预研究的目的是评估fampridine治疗后功能性手和步行测量值的变化,在通过扩展残疾状况量表(EDSS)进行分层后。我们还希望研究不同的功能测量结果,以评估其检测具有临床相关改善的fampridine应答者的能力。
方法:患者从欧登塞大学医院MS诊所招募,根据EDSS评分(中度EDSS(EDSSMod)4.5-5.5[n=19]和重度EDSS(EDSSSev)6.0-7.0[n=14])分为两组。在基线(访问1),他们完成了定时25英尺步行(T25FW),2分钟步行测试(2MWT),九固定钉试验(9HPT),12项多发性硬化症步行量表(MSWS-12),和六点步骤测试(SSST)。参与者每天两次服用10mg的氨吡啶,持续14天,然后进行重新测试(第2次访问)。对于每个测量,截断值用于定义与治疗有临床相关改善的应答者.分别和组合评估测量结果。
结果:在33名参与者中,25例(75.8%)被鉴定为具有临床相关的改善(CRI)。对于所有合并(EDSSAll)的患者,5项测量均显示治疗后功能明显改善.对于单个测量,在接受fampridine治疗14天后,参与者的缓解率最高的是MSWS-12(57.6%)和2MWT(42.4%).从访问1到访问2,2MWT还显示出最大的性能改进(18.5%)。对于重度残疾患者(EDSSSev),在T25FW上的fampridine治疗后没有看到显著的改善,T25FW的大多数响应者有中度残疾(EDSSMod,71.5%)。相反,对于SSST,大多数应答者是EDSSSev(83.3%)。没有参与者对9HPT有临床相关的改善。T25FW的组合,SSST,MSWS-12在区分响应者和非响应者方面不太敏感,而2MWT和MSWS-12的组合识别出相同的应答者,并且可以更好地区分fampridine应答者和非应答者。
结论:EDSS水平不影响fampridine治疗对功能性手和步行措施的影响,并且在中度和重度EDSS水平之间,测量的反应性差异仅很小。自报告步行能力(MSWS-12)和步行耐力(2MWT)的组合优于T25FW,SSST,和MSWS-12在检测到有临床意义的改善后,这可以证明在fampridine治疗期间对MS行走障碍的临床监测是有用的。
OBJECTIVE: The purpose of this interventional
study on participants with multiple sclerosis (MS) with walking disability was to evaluate changes in functional hand and walking measurements after fampridine treatment, after stratifying by the Expanded Disability Status Scale (EDSS). We furthermore wanted to investigate different functional measurements to evaluate their ability to detect responders to fampridine with a clinically relevant improvement.
METHODS: Patients were recruited from the MS Clinic at Odense University Hospital and were classified into two disability groups based on their EDSS score (moderate EDSS (EDSSMod) 4.5-5.5 [n = 19] and severe EDSS (EDSSSev) 6.0-7.0 [n = 14]). At baseline (visit 1) they completed the Timed 25-Foot Walk (T25FW), 2-Minute Walk Test (2MWT), Nine Hold Peg Test (9HPT), 12-item Multiple Sclerosis Walking Scale (MSWS-12), and the Six Spot Step Test (SSST). Participants were given 10 mg twice daily fampridine for 14 days before retested (visit 2). For each measurement, cut-off values were used to define responders with a clinically relevant improvement to treatment. The measurements were evaluated separately and in combination.
RESULTS: Of the 33 participants, 25 (75.8%) were identified as having a clinically relevant improvement (CRI). For all patients combined (EDSSAll), all five measurements showed significant functional improvement after treatment. For the individual measurements, the highest participant response rates after 14 days of fampridine treatment were seen on the MSWS-12 (57.6%) and 2MWT (42.4%). The 2MWT also showed the largest performance improvement (18.5%) from visit 1 to visit 2. For patients with severe disability (EDSSSev), no significant improvement was seen after fampridine treatment on the T25FW, and most of the responders to T25FW had moderate disability (EDSSMod, 71.5%). Conversely for the SSST, most responders were EDSSSev (83.3%). No participants had a clinically relevant improvement on the 9HPT. The combination of T25FW, SSST, and MSWS-12 was less sensitive in distinguishing responders from non-responders, whereas the combination of 2MWT and MSWS-12 identified the same responders and could better distinguish fampridine responders from non-responders.
CONCLUSIONS: EDSS level did not influence the effect of fampridine treatment on functional hand and walking measures and the responsiveness of the measurements differed only a little between moderate and severe EDSS levels. The combination of self-reported walking capacity (MSWS-12) and walking endurance (2MWT) was better than T25FW, SSST, and MSWS-12 at detecting clinically meaningful improvement after fampridine treatment, which could prove useful in the clinical monitoring of walking disabilities in MS during fampridine treatment.