1、ALS关键时期的关键治疗关键时期的关键治疗复旦大学华山医院复旦大学华山医院蒋雨平蒋雨平Ravitts等等100例有上、下运动神经元病所致的例有上、下运动神经元病所致的ALS分析分析平均年龄平均年龄62岁（岁（2685岁）。男性岁）。男性58%，女性，女性42%。92%散发性，散发性，8%为家族性。为家族性。诊断前症状时间平均为诊断前症状时间平均为11月（月（336月）月）延髓发病为延髓发病为29%。单上肢。单上肢34%（右（右24%，左，左10%）。）。躯干占躯干占6%。单下肢。单下肢29%（右（右13%，左，左15%）。）。双侧肢体占双侧肢体占1%。不能分型者占。不能分型者占2%。延髓和上肢
2、病情进展比躯干和下肢快，恶化严重。延髓和上肢病情进展比躯干和下肢快，恶化严重。288例例ALS各亚型存活时间（各亚型存活时间（Tomik等等2006)单上肢型单上肢型单下肢型单下肢型进行性延髓麻痹进行性延髓麻痹单肢型单肢型偏侧型偏侧型比率比率10%90%男男/女女5.3/13.6/11.5/1平均病程平均病程(月月)74.253.142.158.2就诊后平均存就诊后平均存活活(月月)34.22928.743.7 关键时期诊断的要点-找到肯定的运动神经元损害的依据 及早找到“治疗窗”216/301试验的综合分析，降低风险35%。最新研究数据，降低风险67%。利鲁唑组（利鲁唑组（n=17n=17）
3、CTXCTX组（组（n=7n=7）治疗前治疗前治疗后治疗后治疗前治疗前治疗后治疗后NAA/CrNAA/Cr1.851.850.160.161.931.930.160.16*1.941.940.170.171.921.920.160.16Cho/CrCho/Cr1.031.030.110.111.021.020.100.101.061.060.090.091.091.090.150.15利鲁唑组和利鲁唑组和CTXCTX组组1 1H-MRSH-MRS检查随访结果检查随访结果（NAA/CrNAA/Cr和和Cho/CrCho/Cr比值以比值以X XS S表示）表示）*利鲁唑组利鲁唑组NAA/CrNAA
4、/Cr比值治疗前后比较比值治疗前后比较:P0.05,:P0.05,有统计学差异有统计学差异.利鲁唑组利鲁唑组CTXCTX组组治疗前治疗前治疗后治疗后治疗前治疗前治疗后治疗后ALS-FRSALS-FRS评分评分33.5333.536.106.1033.7033.706.406.4032.4332.438.028.0232.2932.297.897.89AppelAppel评分评分44.9444.9417.5917.5932.4332.438.028.0248.4348.4320.1120.1149.0049.0020.2620.26利鲁唑和利鲁唑和CTXCTX治疗治疗ALSALS病的两组临床评分
5、比较病的两组临床评分比较两组治疗前后比两组治疗前后比P0.05.P0.05.在利鲁唑组和在利鲁唑组和AppelAppel量表量表-延髓部分评分随访由治疗前的延髓部分评分随访由治疗前的9.059.055.295.29改善至改善至8.238.234.29,P0.054.29,P0.05。利鲁唑组（利鲁唑组（n=10n=10）免疫治疗组（免疫治疗组（n=7n=7）治疗前治疗前治疗后治疗后治疗前治疗前治疗后治疗后血浆谷氨酸浓度血浆谷氨酸浓度251.35251.3554.3754.37205.74205.7455.3355.33*261.89261.8950.0150.01228.07228.0748.
6、6348.63不同治疗组对血浆谷氨酸浓度的影响不同治疗组对血浆谷氨酸浓度的影响 （浓度单位为（浓度单位为molmolL L-1-1)*利鲁唑组治疗前后血浆谷氨酸浓度下降利鲁唑组治疗前后血浆谷氨酸浓度下降,P0.05,P5yrsEldepryl inhibitor,USAAcetylcysteine24 N-=110 Death,Antioxidant negative The Netherlands 50mg/kg/day sc tracheostomy Follow-up 12 months CoenzymeQ10105N=185ALSFRSrMitochondrialcofactor,an
7、tioxidantIncludesFVC60%andSymptomonset 5yearsUSAPhase 9 months studyperiodVerapamil104 N=72 MVIC and pulmonary Antioxidant negative Treatment function effect compared to USA 3 months lead-Calcium natural history lead-in in,6 months channel period treatment,3 blocker months post-treatment Creatine 41
8、 N:175 Death,tracheostomy Energy negative metabolism The Netherlands 16 months follow-up,sequential design Creatine42 N=104 MVIC in 8 arm Energy Negative,well muscles metabolism tolerated USA 5gms PO QD 6 months follow-up Creatine105 n=156 MVIC,Energy Includes disease change in metabolism duration 5
9、 years USA Phase III arm strength 10gms for 5 d,5 gms thereafter study period 9 monthsNimodipine103 N=87 MVIC and pulmonary Antioxidant negative function USA Mitigating excitotoxicity IGF-I 56 266 Appel scores neurotrophic Functional decline significantly less in USA 9 months high-dose group 0.05 or
10、 0.1mg/kd/day sc IGF-I 57 N=183 Appel scores neurotrophic Negative result.US results not confirmed.Europe 9 months Review combining both trials suggests IGF-1:placebo modest effect43.randomization=Third trial ongoing.2:1 0.1mg/kg/day scBDNF 52 N=1135 6 months FVC neurotrophic Primary analysis negati
11、ve,but benefit USA 6 months study in secondary period analyses;25 or 100pg/kg Low event rate sc Exclusion ALSFRS18,FVC60%SR 57746A N=867 Death/tracheostomy neurotrophic negative,but non-and VC significant beneficial Xaliproden.61 18 months effect on VC for 2rug follow-up arm multinationa 1mg or 2mg
12、QD,Excluded FVC5 yrsSR 57746A N=1210 Death/tracheostomy neurotrophic Overall negative,but and VC trend towardsXaliproden.61 18 months beneficial effect of follow-up 1mg on VC multinational 1mg or 2rug QD,Excluded FVC5 yrs 50mg BID IGF-1105 N=330 MMT Neurotrophic Includes FVC60%agent predicted,USA Ph
13、ase III progressive motor weakness onset Study period 2 years 24 months CNTF 58 N=730 MVlC change neurotrophic Excluded ALSFRS5 yrs 15 or 30 pg/kg No benefit sc TIW Side effects include anorexia,weight loss,cough CNTF.59 N:570 MVIC and FVC neurotrophic Excluded ALS3 yrs,change combined FVC75%predicted,USAPhase IIIDisease duration 3 years 4 months lead in,9 months study period
