利鲁唑组比值治疗前后比较课件

利利鲁唑组比比值治治疗前后比前后比较利鲁唑组比值治疗前后比较利鲁唑组比值治疗前后比较利鲁唑组比值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。诊断前病症时间平均为诊断前病症时间平均为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。2021/1/122Ravitts等100例有上、下运动神经元病所致的ALS分析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)34.22928.743.72021/1/123288例ALS各亚型存活时间Tomik等2006)单上肢型关键时期诊断的要点-找到肯定的运动神经元损害的根据及早找到“治疗窗2021/1/124关键时期诊断的要点-找到肯定的运动神经元损害的根据202216/301试验的综合分析，降低风险35%。最新研究数据，降低风险67%。2021/1/125216/301试验的综合分析，降低风险35%。2021/1/利鲁唑组（利鲁唑组（n=17n=17）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/Cr1.850.161.850.161.930.16*1.930.16*1.940.171.940.171.920.161.920.16Cho/CrCho/Cr1.030.111.030.111.020.101.020.101.060.091.060.091.090.151.090.15利鲁唑组和利鲁唑组和CTXCTX组组1H-MRS1H-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XSXS表示表示*利鲁唑组利鲁唑组NAA/CrNAA/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.2021/1/126利鲁唑组（n=17）CTX组（n=7）治疗前治疗后治疗前治疗利鲁唑组利鲁唑组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33.536.1033.536.1033.706.4033.706.4032.438.0232.438.0232.297.8932.297.89AppelAppel评分评分44.9417.5944.9417.5932.438.0232.438.0248.4320.1148.4320.1149.0020.2649.0020.26利鲁唑和利鲁唑和CTXCTX治疗治疗ALSALS病的两组临床评分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9.055.299.055.29改善至改善至8.234.29,P0.058.234.29,P5yrsEldepryl inhibitor,USA2021/1/1221Selegiline25 N=133 Acetylcysteine24 N-=110 Death,Antioxidant negative The Netherlands 50mg/kg/day sc tracheostomy Follow-up 12 months 2021/1/1222Acetylcysteine24 N-=110 CoenzymeQ10105N=185ALSFRSrMitochondrialcofactor,antioxidantIncludesFVC60%andSymptomonset 5yearsUSAPhase 9 months studyperiod2021/1/1223CoenzymeQ10105N=185ALSFRSrMitoVerapamil104 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 2021/1/1224Verapamil104 N=72 Creatine 41 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 years USA Phase III arm strength 10gms for 5 d,5 gms thereafter study period 9 months2021/1/1225Creatine41 N:1Nimodipine103 N=87 MVIC and pulmonary Antioxidant negative function USA Mitigating excitotoxicity 2021/1/1226Nimodipine103 N=87 IGF-I 56 266 Appel scores neurotrophic Functional decline significantly less in USA 9 months high-dose group 0.05 orIGF-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 sc2021/1/1227IGF-I56 266 BDNF 52 N=1135 6 months FVC neurotrophic Primary analysis negative,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 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 2021/1/1228BDNF52 N=1135 IGF-1105 N=330 MMT Neurotrophic Includes FVC60%agent predicted,USA Phase III progressive motor weakness onset Study period 2 years 24 months 2021/1/1229IGF-1105 N=330 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 period2021/1/1233Minocycline105N=400ALSFRSrAntiThalidomid Thalidomid 治疗治疗ALSALS的二期开放临床试验的二期开放临床试验动物试验中应用动物试验中应用thalidomid thalidomid 减少体内减少体内TNF-TNF-的程度，的程度，延长延长ALSALS动物模型的生存期，是一个很好的动物模型的生存期，是一个很好的TNF-TNF-抑制剂。抑制剂。ALSALS患者每日用患者每日用thalidomid 400mgthalidomid 400mg。23 ALS 23 ALS 仅有仅有1818人完成整个试验人完成整个试验评定指标评定指标ALSALS功能评分功能评分ALSFRSALSFRS和肺功能、疾病进展和肺功能、疾病进展性生命质量评分、不良反响、血清、性生命质量评分、不良反响、血清、cytokinecytokine测定。测定。结果：无效，并有不良反响。结果：无效，并有不良反响。Stommel EWStommel EW等等.Amyotroph Lateral Scler.Amyotroph Lateral Scler,28:1-12,28:1-122021/1/1234Thalidomid 治疗ALS的二期开放临床试验动物试验高压氧气治疗ALS期试验无效Amyotroph Lateral Scler Other Moror Neuron Disord.Amyotroph Lateral Scler Other Moror Neuron Disord.2004,5:250-2542004,5:250-2542021/1/1235高压氧气治疗ALS期试验无效Amyotroph Later谢谢大家！谢谢大家！内容总结利鲁唑组比值治疗前后比较。两者减少组织内ROX)阻止凋亡途路，阻止毒物对细胞存。Gribkoff.VE.。侧脑室角处的神经无死亡减少，星形胶质化减少。评定指标ALS功能评分ALSFRS和肺功能、疾病进展。谢谢大家内容总结利鲁唑组比值治疗前后比较。两者减少组织内ROX)