利鲁唑组比值治疗前后比较课件

1、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治疗前后比较Ravitts等100例有上、下运动神经元病所致的ALS分析平均年龄62岁2685岁。男性58%，女性42%。92%散发性，8%为家族性。诊断前病症时间平均为11月336月延髓发病为29%。单上肢34%右24%，左10%。躯干占6%。单下肢29%右13%，左15%。双侧肢体占1%。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。2021/1/122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100例有上、下运动神经元病所致的ALS分析平均年龄62岁2685岁。男性58%，女性4

2、2%。92%散发性，8%为家族性。诊断前病症时间平均为11月336月延髓发病为29%。单上肢34%右24%，左10%。躯干占6%。单下肢29%右13%，左15%。双侧肢体占1%。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。2021/1/122Ravitts等100例有上、下运动神经元病所致的ALS分析288例ALS各亚型存活时间Tomik等2006)单上肢型单下肢型进行性延髓麻痹单肢型偏侧型比率10%90%男/女5.3/13.6/11.5/1平均病程(月)74.253.142.158.2就诊后平均存活(月)34.22928.743.72021/1/123288例ALS各亚型存

3、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（n=17）CTX组（n=7）治疗前治疗后治疗前治疗后NAA/Cr1.850.161.930.16*1.940.171.920.16Cho/Cr1.030.111.020.101.060.091.090.15利鲁唑组和CTX组1H-MRS检查随访结果NAA/

4、Cr和Cho/Cr比值以XS表示*利鲁唑组NAA/Cr比值治疗前后比较:P0.05,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CTX组治疗前治疗后治疗前治疗后ALS-FRS评分33.536.1033.706.4032.438.0232.297.89Appel评分44.9417.5932.438.0248.4320.1149.0020.26利鲁唑和CTX治疗ALS病的两组临床评分比较两组治疗前后比P0.05.在利鲁唑组和Appel量表-延髓部分评分随访由治疗前的9.055.29改善至8.234.29,P5yrsEldepryl inhi

5、bitor, 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 mo

6、nths 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

7、N=72 Creatine41 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 m

8、etabolism 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-I56 266 Appel scores neurotrophic Fu

9、nctional 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 sc2021/1/1227IG

10、F-I56 266 BDNF52 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 Xalip

11、roden.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

12、 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 CNTF58 N=730 MVlC change neurotrophic Excluded ALSFRS5 yrs 15 or 30 pg/kg No benefit sc TIW

13、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 治疗ALS的二期开放临床试验动物试验中应用thalidomid 减少体内TNF-的程度，延长ALS动物模型的生存期，是一个很好的TNF-抑制剂。ALS患者每日用thalidomid 400mg。23 ALS 仅有18人完成整个试验评定指标ALS功能评分ALSFRS和肺功能、疾病进展性生命质量评分、不良反响、血清、cytokine测定。结果：无效，并有不良反响。 Stommel EW等. Amyotroph Lateral Scler, 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 N