Noseworthy J H, O'Brien P C, Weinshenker B G, Weis J A, Petterson T M, Erickson B J, Windebank A J, Whisnant J P, Stolp-Smith K A, Harper C M, Low P A, Romme L J, Johnson M, An K N, Rodriguez M
Department of Neurology, Mayo Clinic, Rochester, MN 55905, USA.
Neurology. 2000 Oct 24;55(8):1135-43. doi: 10.1212/wnl.55.8.1135.
Immunoglobulin (Ig) administration induces remyelination in the Theiler's virus model of MS.
A randomized, double-blinded, placebo-controlled trial of IV immunoglobulin (IVIg) was performed in patients with MS who had persistent muscle weakness that had been stable for between 4 and 18 months to determine whether this would improve muscle strength (primary outcome: isometric muscle strength). Patients received either IVIg (0.4 g/kg) or placebo daily for 5 days, then single infusions every 2 weeks for 3 months (total, 11 infusions). Muscle groups identified by clinical measures to have unchanging significant weakness were the major targets for therapeutic response (targeted neurologic deficit [TND]).
IVIg was well tolerated. An interim analysis after 67 patients were enrolled indicated no difference in the degree of change in strength between treatment groups in either the TND or non-TND muscle groups at 6 months, and the trial was terminated. There was no apparent benefit in relapse behavior or impairment measures during the 6-month observation period. Nor was there apparent benefit in either patients who remained clinically stable or in those with evidence of disease activity. Patients with active MS during the trial worsened in both TND and non-TND muscle groups. This worsening was seen regardless of whether the clinical manifestations of disease activity involved the TND muscle groups.
IVIg does not reverse established weakness in MS. Measurements of isometric muscle strength were reliable (reproducible) indices of strength and may be sensitive, objective methods to document functional changes in impairment in future MS trials.
在多发性硬化症的泰勒氏病毒模型中，免疫球蛋白（Ig）给药可诱导髓鞘再生。
对患有持续肌肉无力且病情稳定4至18个月的多发性硬化症患者进行了一项静脉注射免疫球蛋白（IVIg）的随机、双盲、安慰剂对照试验，以确定这是否能改善肌肉力量（主要结局：等长肌肉力量）。患者每天接受IVIg（0.4 g/kg）或安慰剂治疗，持续5天，然后每2周进行一次单次输注，共3个月（总计11次输注）。通过临床测量确定存在持续明显无力的肌肉群是治疗反应的主要目标（靶向神经功能缺损[TND]）。
IVIg耐受性良好。在纳入67例患者后进行的中期分析表明，6个月时，治疗组在TND或非TND肌肉群中的力量变化程度无差异，试验终止。在6个月的观察期内，复发行为或损伤测量方面没有明显益处。无论是临床保持稳定的患者还是有疾病活动证据的患者，均未显示出明显益处。试验期间患有活动性多发性硬化症的患者在TND和非TND肌肉群中均出现恶化。无论疾病活动的临床表现是否涉及TND肌肉群，均出现这种恶化情况。
IVIg不能逆转多发性硬化症已有的肌无力。等长肌肉力量测量是可靠（可重复）的力量指标，可能是未来多发性硬化症试验中记录功能损伤变化的敏感、客观方法。
