多发性硬化症核间性眼肌麻痹的治疗:一项随机、双盲、安慰剂对照交叉试验。
Treatment of internuclear ophthalmoparesis in multiple sclerosis with fampridine: A randomized double-blind, placebo-controlled cross-over trial.
机构信息
Centre for Human Drug Research, Leiden, the Netherlands.
Department of Ophthalmology, Neuro-ophthalmology Expertise Center, Amsterdam UMC, Amsterdam, the Netherlands.
出版信息
CNS Neurosci Ther. 2019 Jun;25(6):697-703. doi: 10.1111/cns.13096. Epub 2019 Feb 12.
AIM
To examine whether the velocity of saccadic eye movements in internuclear ophthalmoparesis (INO) improves with fampridine treatment in patients with multiple sclerosis (MS).
METHODS
Randomized, double-blind, placebo-controlled, cross-over trial with fampridine in patients with MS and INO. Horizontal saccades were recorded at baseline and at multiple time points post-dose. Main outcome measures were the change of peak velocity versional dysconjugacy index (PV-VDI) and first-pass amplitude VDI (FPA-VDI). Both parameters were compared between fampridine and placebo using a mixed model analysis of variance taking patients as their own control. Pharmacokinetics was determined by serial blood sampling.
RESULTS
Thirteen patients had a bilateral and 10 had a unilateral INO. One patient had an INO of abduction (posterior INO of Lutz) and was excluded. Fampridine significantly reduced both PV-VDI (-17.4%, 95% CI: -22.4%, -12.1%; P < 0.0001) and FPA-VDI (-12.5%, 95% CI: -18.9%, -5.5%; P < 0.01). Pharmacokinetics demonstrated that testing coincided with the average t at 2.08 hours (SD 45 minutes). The main adverse event reported after administration of fampridine was dizziness (61%).
CONCLUSION
Fampridine improves saccadic eye movements due to INO in MS. Treatment response to fampridine may gauge patient selection for inclusion to remyelination strategies in MS using saccadic eye movements as primary outcome measure.
目的
观察在多发性硬化症(MS)患者中,应用苯丁胺能否改善核间性眼肌麻痹(INO)的眼球扫视速度。
方法
这是一项在 MS 合并 INO 患者中进行的、随机、双盲、安慰剂对照、交叉试验,使用苯丁胺治疗。在基线和多次给药后时间点记录水平扫视。主要观察指标是扫视速度变化的偏共轭指数(PV-VDI)和首次通过振幅 VDI(FPA-VDI)。使用混合模型方差分析,将患者作为自身对照,比较苯丁胺和安慰剂之间这两个参数的变化。通过连续采血来确定药代动力学。
结果
13 例患者为双侧 INO,10 例为单侧 INO。1 例患者为外展性 INO(Lutz 后部 INO),被排除在外。苯丁胺显著降低了 PV-VDI(-17.4%,95%CI:-22.4%,-12.1%;P<0.0001)和 FPA-VDI(-12.5%,95%CI:-18.9%,-5.5%;P<0.01)。药代动力学显示,测试时间与平均 t 值(2.08 小时,SD 45 分钟)相符。苯丁胺给药后报告的主要不良事件是头晕(61%)。
结论
苯丁胺可改善 MS 患者因 INO 引起的眼球扫视运动。对苯丁胺的治疗反应可能可以衡量患者是否适合纳入以眼球扫视运动为主要终点的 MS 髓鞘再生策略。