干扰素β-1b对再发缓解型多发性硬化患者脑萎缩影响的MRI定量评估

背景:核磁共振成像的定量测量已被广泛用于评估多发性硬化症的治疗效果。目的:确定是否干扰素β-1b对多发性硬化脑萎缩的影响能通过MRI测量表达出来。设计:随机对照观察。单位:日本京都宇多野病院神经疾病研究中心。对象:选择1998-01/12在在日本京都宇多野病院神经疾病研究中心收治的188例多发性硬化患者,男55例,女133例,年龄16～59岁,平均(36±11)岁。纳入标准:①按poser再发缓解型诊断标准临床确诊为多发性硬化。②扩展残疾状况评分表得分≤7分。③在过去的1年中至少1次复发,或在就诊之前的2年间有至少2次复发,但就诊前30d无复发,神经系统体征稳定至少1个月,干扰素β-1b皮试阴性。④均对检测项目知情同意。纳入患者中,视神经脊髓型148例,经典型50例。方法:①药物治疗:所有患者给予干扰素β-1b注射剂,根据注射剂量不同将患者分为低剂量组(n=93)和高剂量组(n=95),分别给予160万U和800万U隔日干扰素β-1b注射剂皮下注射,共使用2年。②磁共振扫描检查:对所有患者包括病灶的部位(视神经、大脑、小脑、脑干和脊髓)进行磁共振扫描,T1和T2加权轴面磁共振检查由同一神经病学家评估,T2加权像病灶面积是逐层相加计算出总面积以mm2表示,检查指标为第三脑室、侧脑室宽度、脑宽度进行测量,结果采用萎缩率表示。③神经功能缺损检查:采用Kurtzke扩展残疾状况评分表(从0分到10分,0分为正常,分数越高病情越严重)评估。④相关因素分析:对148例典型多发性硬化患者脑萎缩情况和T2病灶面积和扩展残疾状况评分表得分变化两项因素进行相关性分析,同时对起始时变量(年龄,病程,复发率,T2病灶面积和扩展残疾状况评分表得分)和脑萎缩情况进行相关性分析。主要观察指标:①两组患者脑萎缩情况比较。②脑萎缩测量相关因素分析。结果:纳入198例患者全部进入结果分析。①两组患者脑萎缩情况比较结果:高剂量组经典型多发性硬化患者侧脑室宽度、三脑室宽度、脑宽度萎缩率分别是2.84%,3.15%和1.3%,明显低于低剂量组(4.09%,5.36%,1.97%,P<0.01)。高剂量组视神经脊髓型多发性硬化患者侧脑室宽度、三脑室宽度、脑宽度的萎缩率分别是0.9%,1.55%和0.6%,与低剂量组无明显差异(1.65%,1.75%,0.7%,P>0.05)。②经典型多发性硬化患者侧脑室宽度与T2病灶面积和EDSS得分均有明显相关性(r=0.33,0.27,P<0.01),三脑室宽度与T2病灶面积和EDSS得分有明显相关性(r=0.31,0.29,P<0.05),脑宽度与T2病灶面积和EDSS得分也有明显相关性(r=0.11,0.14,P<0.05),起始时EDSS得分和T2病灶面积变化与侧脑室宽度明显相关(r=0.23,0.33,P<0.05),其他起始时的参数未能显示出有意义的关系。结论:干扰素β-1b对脑萎缩的影响是有积极意义的,在高和低剂量组之间,有意义的差别被显示出来。脑萎缩测量提供了一个独立的关于干扰素β-1b治疗多发性硬化的肯定作用和剂量的影响。

Quantitative evaluation of influences of interferon beta-1b on brain atrophy in relapsing-remitting multiple sclerosis patients with magnetic resonance imaging

BACKGROUND: The quantitative measurements based on magnetic resonance imaging (MRI) have been vastly used in evaluating the therapeutic efficacy on multiple sclerosis (MS).OBJ ECTIVE: To determine whether the effect of IFNB-1b on brain atrophy of MS could be shown with analysis of MRI measurement.DESIGN: Randomized controlled observation.SETTING : Center for Neurological Diseases, Utano National Hospital.PARTICIPANTS: Totally 188 patients with MS, including 55 males and 133 females aged from 16-59 years, averagely(36±11) years, from Center for Neurological Diseases, UtanoNational Hospital from January to December 1998 were enrolled. Inclusive criteria: ①according to Poser RR type criteria were considered as having MS for enrollment, ②Expanded Disability Status Scale (EDSS) score of 7.0 or less, ③at least 1 relapse in the past year or at least 2 relapses in the past two years prior to enrollment, but no relapse for 30 days before enrollment, stable neurological state for at least 1 month and negative results of the IFNB-1b needle-prick test, and ④they all knew the detected items and agreed. In the included patients, there were 148 cases of optic nerves and spinal cord type and 40 cases of classical type.METHODS: ①Drug treatment: All the patients were treated with IFNB-1b injectable preparation (provided by Japanese Pharmaceuticals Company). According to the different injected dosage, the patients were divided into low-dosage group (n =93) and high-dosage group (n =95), given with 1.6 million U and 8 million U of IFNB-1b subcutaneously on alternate days for 2 years. ②MRI examination: The patients received MRI in lesion site (optic nerves, cerebrum, cerebellum, brainstem, and spinal cord). T1 and T2-weighted axial MRI scan were performed by a single neurologist. The area of the MS lesions in T2-weighted images was summed slice by slice for a total lesion area and was recorded as mm2. Third ventricle, lateral ventricle width and brain width were measured and expressed by atrophy rate. ③Neurologic impairment examination: Neurologic impairment was evaluated with Kurtzke EDSS (from 0 point to 10 points, 0 point as normal, the higher score represented severe condition). ④Analysis of related factors: Correlation analysis was performed in brain atrophy condition and T2 focus area with EDSS score in 148 MS patients with typical MS. At the same time,correlation analysis was conducted between variance (age, progress, relapse rate, T2 focus area and EDSS score) and brain atrophy.MAIN OUTCOME MEASURES: ①Comparison of brain atrophy in patients of the two groups, and ②analysis of related factors of brain atrophy measurements.RESULTS: Totally 188 patients were involved in the result analysis. ①Outcome of brain atrophy comparison in the two groups: In classical type MS the rates of atrophy measures in high-dosage group were 2.84%, 3.15%, and 1.3% in lateral ventricle width, third ventricle width and brain width, respectively, and significantly lower than those in low-dosage group (4.09%, 5.36% and 1.97%, P ＜ 0.01). In optic nerve and spinal cord type MS patients, the rates of brain atrophy were 0.9%, 1.55% and 0.6% in lateral ventricle width, third ventricle width and brain width, respectively in high-dosage group, and there was no significant difference as compared with the low-dosage group (1.65%, 1.75% and 0.7%, P ＜0.05). ②There was significant correlation of lateral ventricle width, T2 focus area and EDSS score in classical MS patients (r =0.33,0.27, P ＜ 0.01 ). There was significant correlation of third ventricle width, T2 focus area and EDSS score (r=0.31,0.29, P ＜ 0.05). There was significant correlation of brain width, T2 focus area and EDSS score (r =0.11,0.14, P ＜0.05). There was significant correlation of baseline EDSS score and T2 focus area with lateral ventricle width (r =0.23,0.33, P ＜ 0.05). The other baseline variables failed to show a significant contribution to the process.CONCLUSION: The effects of IFNB-1b on brain atrophy were positive and significant differences were also found between both high- and low-dosage groups. This brain atrophy measurement provides an independent MRI confirmation of a therapy and dose effect of IFNB-1b for MS.