利魯唑組比值治療前后比較課件

1、利魯唑組比值治療前后比較利魯唑組比值治療前后比較利魯唑組比值治療前后比較Ravitts等100例有上、下運動神經(jīng)元病所致的ALS分析平均年齡62歲2685歲。男性58%，女性42%。92%散發(fā)性，8%為家族性。診斷前病癥時間平均為11月336月延髓發(fā)病為29%。單上肢34%右24%，左10%。軀干占6%。單下肢29%右13%，左15%。雙側(cè)肢體占1%。不能分型者占2%。延髓和上肢病情進展比軀干和下肢快，惡化嚴重。2021/1/122利魯唑組比值治療前后比較利魯唑組比值治療前后比較利魯唑組比值Ravitts等100例有上、下運動神經(jīng)元病所致的ALS分析平均年齡62歲2685歲。男性58%，女性4

2、2%。92%散發(fā)性，8%為家族性。診斷前病癥時間平均為11月336月延髓發(fā)病為29%。單上肢34%右24%，左10%。軀干占6%。單下肢29%右13%，左15%。雙側(cè)肢體占1%。不能分型者占2%。延髓和上肢病情進展比軀干和下肢快，惡化嚴重。2021/1/122Ravitts等100例有上、下運動神經(jīng)元病所致的ALS分析288例ALS各亞型存活時間Tomik等2006)單上肢型單下肢型進行性延髓麻痹單肢型偏側(cè)型比率10%90%男/女5.3/13.6/11.5/1平均病程(月)74.253.142.158.2就診后平均存活(月)34.22928.743.72021/1/123288例ALS各亞型存

3、活時間Tomik等2006)單上肢型關(guān)鍵時期診斷的要點-找到肯定的運動神經(jīng)元損害的根據(jù)及早找到“治療窗2021/1/124關(guān)鍵時期診斷的要點-找到肯定的運動神經(jīng)元損害的根據(jù)202216/301試驗的綜合分析，降低風險35%。最新研究數(shù)據(jù)，降低風險67%。2021/1/125216/301試驗的綜合分析，降低風險35%。2021/1/利魯唑組（n=17）CTX組（n=7）治療前治療后治療前治療后NAA/Cr1.850.161.930.16*1.940.171.920.16Cho/Cr1.030.111.020.101.060.091.090.15利魯唑組和CTX組1H-MRS檢查隨訪結(jié)果NAA/

4、Cr和Cho/Cr比值以XS表示*利魯唑組NAA/Cr比值治療前后比較:P0.05,有統(tǒng)計學(xué)差異.2021/1/126利魯唑組（n=17）CTX組（n=7）治療前治療后治療前治療利魯唑組CTX組治療前治療后治療前治療后ALS-FRS評分33.536.1033.706.4032.438.0232.297.89Appel評分44.9417.5932.438.0248.4320.1149.0020.26利魯唑和CTX治療ALS病的兩組臨床評分比較兩組治療前后比P0.05.在利魯唑組和Appel量表-延髓部分評分隨訪由治療前的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 治療ALS的二期開放臨床試驗動物試驗中應(yīng)用thalidomid 減少體內(nèi)TNF-的程度，延長ALS動物模型的生存期，是一個很好的TNF-抑制劑。ALS患者每日用thalidomid 400mg。23 ALS 僅有18人完成整個試驗評定指標ALS功能評分ALSFRS和肺功能、疾病進展性生命質(zhì)量評分、不良反響、血清、cytokine測定。結(jié)果：無效，并有不良反響。 Stommel EW等. Amyotroph Lateral Scler, 28:1-122021/1/1234Thalidomid 治療ALS的二期開放臨床試驗動物試驗高壓氧氣治療ALS期試驗無效Amyotroph Lateral Scler Other Moror N