脊髓損傷香港課件

1、脊髓損傷 – 臨床上的問題Spinal Cord InjuryThe Clinical Problem,Keith DK LukChair Professor & HeadDept of Orthopedics & TraumatologyUniversity of Hong Kong,Anatomy 解剖學(xué),脊髓 中樞神經(jīng)系統(tǒng)Spinal cord (central nervous system) v

2、s 馬尾叢 周邊神經(jīng)系統(tǒng)Cauda equina(peripheral nervous system),,C1 to L1,,,L2 to S4,,脊髓損傷的發(fā)病率 Incidence of Spinal Cord Injury,在美國(guó)，每百萬人口約有40宗新病例　 (每年10,000宗病例)40 new cases / million population in USA 　(about 10,000 cases

3、 per year)　在歐洲, 臺(tái)灣及香港，每百萬人口約有20宗新病例20 new cases / million population in Europe, Taiwan & Hong Kong 　　National Spinal Injury Statistical Center, USA. 2004http://www.spinalcord.uab.edu,一九九八至九九年度衛(wèi)生署年報(bào)Department

4、 of Health Annual Report 1998/99,脊髓損傷 – 365 病人Spinal Cord Injury – 365 patients,2000年衛(wèi)生署資料Department of Health Website Information,脊髓及神經(jīng)受損 – 452 病人Injury to nerves and spinal cord – 452 patients,嚴(yán)重脊髓損傷 More Severe SC

5、I,二零零四年上半年共有71個(gè)病例First 6 months/200471 cases,常見脊髓損傷的原因Common causes of spinal cord injury,交通意外Motor vehicular accident高處墜下 Fall from height運(yùn)動(dòng)創(chuàng)傷 Sports & recreational injuries暴力 Violence,香港常見導(dǎo)致脊髓受損

6、的原因Common Causes of Spinal Cord Impairment in Hong Kong,退化病 Degenerative diseases創(chuàng)傷 Traumatic injuries腫瘤性疾病 Neoplastic diseases發(fā)炎性疾病 Inflammatory diseases,殘疾的程度Disability relates to:,受損水平 Leve

7、l of injury四肢癱瘓 Quadriplegia下肢癱瘓 Paraplegia,受損程度 Degree of injury部份受損 Incomplete完全受損 Complete,高位脊髓受損High Spinal Cord Injury,依賴呼吸機(jī) Ventilator dependent呼吸併發(fā)癥 Respiratory complication完全

8、依賴 Totally dependent,臨床問題 Clinical Problems,生理問題 Physical 心理問題 – 病人, 家屬 Psychological – Patient, Family社交問題 – 就業(yè), 參與社會(huì)活動(dòng) Socio-economical – Employment, Community access,,生理問題Physical Problems,喪失活動(dòng)能

9、力 Loss of motion失去感覺 Loss of sensation - Pressure ulcers 褥瘡 痛楚 Pain,生理問題Physical Problems,交感神經(jīng)功能 Autonomic dysreflexia - 膀胱 – 尿滯留或小便失禁 Bladder – retention or inc

10、ontinence - 大腸 – 便秘或失禁 Bowel – constipation or incontinence - 功能性障礙 Sexual dysfunction 痙攣 Spasticity,完全癱瘓者:一年內(nèi):約5-10%的病人約有兩節(jié)段的改善90% 的病人有一節(jié)段的改善 少於1%的病人有兩節(jié)段以上的改善: For complete SCI:In one year

11、:90% of SCI patients improve one level. ~5-10% of SCI patients improve two levels. less than 1% of SCI patients improve more than two levels半癱瘓者: 比較難估計(jì), 不過整體比完全癱瘓者優(yōu)勝For incomplete SCI less predictable, tends to b

12、e better than complete injuries NSCISC, 2004. http://www.spinalcord.uab.edu,Natural history,傳統(tǒng)的療法 Conventional management,脊髓是不能被修補(bǔ)或再生 Repair, regeneration of the spinal

13、 cord is not possible集中復(fù)康治療主流治療方向增強(qiáng)殘餘功能恢復(fù)功能 減低傷殘 Focus on rehabilitationMain stream managementMaximize residual functionsFunctional restoration Minimize disabilities,截癱性步行 Paraplegic walking,半癱瘓 Incomplete

14、 Paraplegia,家居改善 Home modification,公共交通工具 Transportation,,,,香港現(xiàn)有的服務(wù)Current Services in Hong Kong,幾乎所有的脊髓復(fù)康服務(wù)均由醫(yī)院管理局提供 Nearly all spinal cord rehabilitation are provided by HA三間由醫(yī)管局提供的脊髓復(fù)康醫(yī)院 3 SCI units un

15、der the Hospital Authority香港區(qū)：麥理浩復(fù)康院, MacLehose Rehabilitation Centre 九龍區(qū)：九龍醫(yī)院, Kowloon Hospital新界區(qū)：大埔醫(yī)院, Tai Po Hospital高技術(shù)水準(zhǔn)的設(shè)備 - FES, 矯具等State-of- the-art facilitiesFES, orthosis, etc,脊髓損傷的治療及再生的可能Pot

16、ential for spinal cord repair and regeneration,再生療法Regenerative therapies,脊髓損傷研究的重要性 Importance of Spinal Cord Injury (SCI) Research,研究脊髓損傷的病理組織學(xué) To investigate pathohistology of Spinal Cord Injury：,甚麼因素阻止了脊髓損

17、傷後軸突的再生？ What stop axonal regeneration in Spinal Cord Injury?,如何促進(jìn)脊髓損傷受損神經(jīng)元的存活和再生？ How to enhance survival and regeneration of injured neurons in Spinal Cord Injury?,這些問題的答案將會(huì)給脊髓損傷病人提供新的療法。 Answer to the

18、se questions will contribute significantly for the new treatment methods for Spinal Cord Injury patients.,損傷後神經(jīng)元如何、為何死亡？ how and why neurons die after injury?,確定已用於脊髓損傷病人臨床試驗(yàn)的幹細(xì)胞、施萬細(xì)胞以及Oefactory Ensheathing Cells

19、 細(xì)胞(OEC - 嗅鞘上皮細(xì)胞)移植等治療方法的機(jī)制。To confirm and prove mechanisms of treatment methods that have been used in clinical trial study for the Spinal Cord Injury patients, such as stem cell, Schwann’s cell and OEC cell (Oefactory

20、 Ensheathing Cells) transplantations.,為脊髓損傷新藥的檢測(cè)提供動(dòng)物模型。To provide animal models for testing effects of new drugs for Spinal Cord Injury.,Neuroscience Exploring the Brain, Second Edition.Bear MF, Connors BW, Paradiso MA

21、,脊髓的主要功能（Main Functions of the Spinal Cord）,將感覺訊息從外周傳向腦，運(yùn)動(dòng)訊息從腦傳向外周。,構(gòu)成局部回路和反射。 To perform locomotion and reflex.,To convey sensory impulses from periphery to the brain and to convey motor impulses from the brain

22、to the periphery.,神經(jīng)細(xì)胞死亡 （Neuronal cell death） a. 原發(fā)損傷 Primary injury (空洞cavity) b. 繼發(fā)損傷 Secondary injury,,脊髓損傷後有侍解決的問題,2. 軸突切斷（Axotomy）,3. 脫髓鞘（Demyelination）,4. 膠質(zhì)癍痕（Glial scar）,5. 抑制性分子（Inhibit molecules

23、, NI-35, NI-250）,6. 血液供應(yīng)不良（Poor Blood supply）,,,,,,,,,1a,1b,,,,3,,,,,,2,,2,,,,,,,,,,,,,,,,,,,,,,,,,,,,5,2,4,5,6,,脊髓損傷的突破性研究 (一)（Breakthrough Studies on the Field of Spinal Cord Injury）,1. 神經(jīng)細(xì)胞死亡（Neuronal cell death）波尼松

24、龍治療減少細(xì)胞死亡，利用嗅鞘上皮細(xì)胞或幹細(xì)胞移植替代死亡的細(xì)胞。Reduce cell death by therapy with methylprednisolone (Young 1990) and replace death cells with OEC transplantation (Li, J of Neurosci. 1998; Huang, 2003) or Stem cells transplantation (Har

25、per, PNAS 2004).,2. 軸突切斷（Axotomy）的治療增強(qiáng)軸突切斷神經(jīng)元的再生能力。Enhance regeneration ability of axotomized neurons (Pears Nature Medicine, 2004; Yick, J Neurotrauma, 2004).,,,脊髓損傷的突破性研究(二)（Breakthrough Studies on the Field of Spin

26、al Cord Injury）,3. 去髓鞘（Demyelination）的治療通過施萬細(xì)胞移植重建髓鞘 。Rebuild myelination by Schwann’s cell transplantation (Xu, EJN 1999; Sivasankaran, Nature Neurosci. 2004).,,4,5,6. 膠質(zhì)癍痕及抑制性分子（Glial scar and Inhibit molecules）通過改變

27、局部化學(xué)環(huán)境減少癍痕形成，去除抑制因子。Reduce glial scar and remove inhibitor molecules by changing the local chemical environment (Yick, Neuroreport, 2000; Moon, Nature Neurosci. 2001).,,用於治療脊髓損傷的幹細(xì)胞,,Clinical Trials CentreFaculty of Me

28、dicineThe University of Hong Kong,8/F Clinical Pathology BuildingQueen Mary Hospital, Hong KongTel: (852) 2855 4664Fax: (852) 2974 1248E-mail: ctcentre@hkucc.hku.hkwww.hku.hk/ctc,香港大學(xué)醫(yī)學(xué)院臨床試驗(yàn)中心,due to the lack of

29、 investigators and patients in the established regions.,,Study sites,Drug development has become a global activity,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,由於研究員及合適參與臨床試驗(yàn)的病人在已發(fā)展

30、地區(qū)均出現(xiàn)短缺，臨床試驗(yàn)正趨向全球化。,試驗(yàn)場(chǎng)地,,19801990,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,1996,ICH GCP Guideline,良好臨床試驗(yàn)管理規(guī)範(fàn),,,,已發(fā)出之臨床試驗(yàn)證書,,,,,Global clinical trialsInto China and HKfrom o

31、ther regions吸引世界各地之科研機(jī)構(gòu)到中、港進(jìn)行臨床試驗(yàn),Our aim我們的目標(biāo),,,,Products from China and HK協(xié)助中、港之醫(yī)藥產(chǎn)品進(jìn)軍國(guó)際市場(chǎng),,Our aim我們的目標(biāo),Highly qualified clinical investigators 高質(zhì)素之臨床研究員Scientific expertise 科學(xué)專業(yè)知識(shí)Experienced in clinical r

32、esearch 豐富之臨床研究經(jīng)驗(yàn)High population density 高人口密度Excellent infrastructure 優(yōu)良之基建… and more …及其他有利條件,Why Hong Kong? 為何選擇香港?,,,Clinical Sciences –Number of Publications (1991-2002)臨床科學(xué) – 出版數(shù)目 (1991-2002),Clinical Trial /

33、Research Experience 臨床試驗(yàn)/研究經(jīng)驗(yàn),,,Hong Kong Hospital Authority Clusters,,,,,,,,,,HA,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,7 Clusters七個(gè)聯(lián)網(wǎng)43 Hospitals/Institutions四十三間醫(yī)院/機(jī)構(gòu)29,022 Beds

34、二萬九千零二十二個(gè)床位6.8 Million Population六百八十萬人口,香港醫(yī)院管理局聯(lián)網(wǎng),,,Hong Kong Hospital Authority Clusters,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,Compliance with ICH GCP 符合良好臨床試驗(yàn)管理規(guī)範(fàn)之標(biāo)準(zhǔn)

35、Uniform operations 統(tǒng)一運(yùn)作標(biāo)準(zhǔn)HA Guidelines 醫(yī)院管理局指引SOPs 標(biāo)準(zhǔn)運(yùn)作程序Trained EC members 曾受訓(xùn)之倫理委員會(huì)會(huì)員,Ethics Committees 倫理委員會(huì),香港醫(yī)院管理局聯(lián)網(wǎng),Established in 1998 under the Faculty of Medicine of The University of Hong Kong (founded in 18

36、87)於一九九八年在香港大學(xué)醫(yī)學(xué)院之下成立The first full-service Academic Research Organization (ARO) in clinical trials in Asia亞洲首間一站式臨床試驗(yàn)學(xué)術(shù)研究機(jī)構(gòu),Clinical Trials Centre 臨床試驗(yàn)中心,Objective: To offer one-stop solutions to clinical trial spo

37、nsors and investigators,目標(biāo): 提供一站式服務(wù)予臨床試驗(yàn)贊助商及研究員,Organization Structure 組織架構(gòu),Sponsors with a Master Clinical Trial Contract with HKU部份已與香港大學(xué)訂定標(biāo)準(zhǔn)合約之贊助商,Services 服務(wù),,,Clinical Trials 臨床試驗(yàn),CTC – No. of Sponsored Trials Cont

38、racted Per Year受贊助之臨床試驗(yàn)總數(shù)(每年),,,,,Types of Trials by Therapeutic Area按?？品诸?Types of Trials by Trial Phase按臨床試驗(yàn)期分類,,Type of clinical trials 臨床試驗(yàn)之種類,CTC – Types of Trials,腫瘤科,兒科,泌尿科,一期,腸胃及肝臟科,感染及傳染科,血液科,心臟科,其他,內(nèi)分泌及新陳代謝科

39、,三期,四期,其他,二期,精神科,5 clinical laboratories:Anatomical PathologyClinical BiochemistryClinical ImmunologyHaematologyMicrobiology五大臨床實(shí)驗(yàn)室：組織及細(xì)胞病理臨床生化臨床免疫血液微生物學(xué)Fully accredited by the College of American Patho

40、logists (CAP) (under the category of large multidiscipline laboratory),Laboratory Facilities 實(shí)驗(yàn)室設(shè)備,得到美國(guó)病理學(xué)家學(xué)會(huì)(CAP)之認(rèn)証(隸屬大型多功能實(shí)驗(yàn)室組別),Master of Medical Sciences / PgDip / PgCert 醫(yī)療科學(xué)碩士/研究院文憑/研究院證書- Clinical Trials Res

41、earch Methodology 臨床試驗(yàn)研究方法學(xué)- Medical Statistics 統(tǒng)計(jì)分析GCP courses 良好臨床試驗(yàn)管理規(guī)範(fàn)課程EC members training倫理委員會(huì)會(huì)員之培訓(xùn)Symposia / International conferences講座/國(guó)際會(huì)議Web-based Investigators Certification Programme研究員網(wǎng)上訓(xùn)練課程,E

42、ducational Activities 教育活動(dòng),Pre-study activities試驗(yàn)前,Study activities試驗(yàn)中,On the conduct of Clinical Trials臨床試驗(yàn)程序,,Post-study activities試驗(yàn)後,Protocol CRFsInvestigatorTrainingGMPFinanceApprovalsInsurance

43、Logistics,Spinal Cord I. Research脊骨創(chuàng)傷研究,試驗(yàn)方案,研究者培訓(xùn),藥品生產(chǎn)質(zhì)量管理規(guī)範(fàn),財(cái)務(wù),病例報(bào)告表,保險(xiǎn),物流,批核,Pre-study activities試驗(yàn)前,Study activities試驗(yàn)中,,Post-study activities試驗(yàn)後,Site activitiesProject Manag.(QA)Data Manag.Safety Monit

44、oring,研究單位活動(dòng),安全監(jiān)控,項(xiàng)目管理(品質(zhì)保証),數(shù)據(jù)處理,On the conduct of Clinical Trials臨床試驗(yàn)程序,Spinal Cord I. Research脊骨創(chuàng)傷研究,Pre-study activities試驗(yàn)前,Study activities試驗(yàn)中,,Post-study activities試驗(yàn)後,Data Manag.Medical StatisticsMedic