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,脊髓 中樞神經系統Spinal cord (central nervous system) vs 馬尾叢 周邊神經系統Cauda equina(peripheral nervous system),C1 to L1,L2 to S4,脊髓損傷的發病率 Incidence of Spinal
2、Cord Injury,在美國，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 per year)在歐洲, 台灣及香港，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生署年報Depa
3、rtment of Health Annual Report 1998/99,脊髓損傷 365 病人Spinal Cord Injury 365 patients,2000年衛生署資料Department of Health Website Information,脊髓及神經受損 452 病人Injury to nerves and spinal cord 452 patients,嚴重脊髓損傷 More Severe SCI,二零零四年上半年共有71個病例First 6 months/200471 cases,常見脊髓損傷的原因Common causes of spinal cord inj
4、ury,交通意外Motor vehicular accident高處墜下 Fall from height運動創傷 Sports & recreational injuries暴力 Violence,香港常見導致脊髓受損的原因Common Causes of Spinal Cord Impairment in Hong Kong,退化病 Degenerative diseases創傷 Traumatic injuries腫瘤性疾病 Neoplastic diseases發炎性疾病 Inflammatory diseases,殘疾的程度Disability relates to:,受損水平 Le
5、vel 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 Ventilator dependent呼吸併發症 Respiratory complication完全依賴 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, 參與社會活動 S
6、ocio-economical Employment, Community access,生理問題Physical Problems,喪失活動能力 Loss of motion失去感覺 Loss of sensation - Pressure ulcers 褥瘡 痛楚 Pain,生理問題Physical Problems,交感神經功能 Autonomic dysreflexia - 膀胱 尿滯留或小便失禁 Bladder retention or incontinence - 大腸 便秘或失禁 Bowel constipation or incontinence - 功能性障礙 Sexual
7、dysfunction 痙攣 Spasticity,完全癱瘓者:一年內:約5-10%的病人約有兩節段的改善90% 的病人有一節段的改善 少於1%的病人有兩節段以上的改善: For complete SCI:In one year: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, 不過整體比完全癱瘓者優勝For incomplete SCI les
8、s predictable, tends to be better than complete injuries NSCISC, 2004. http:/www.spinalcord.uab.edu,Natural history,傳統的療法 Conventional management,脊髓是不能被修補或再生 Repair, regeneration of the spinal cord is not possible集中復康治療主流治療方向增強殘餘功能恢復功能 減低傷殘 Focus on rehabilitationMain stream managementMaximize resid
9、ual functionsFunctional restoration Minimize disabilities,截癱性步行 Paraplegic walking,半癱瘓 Incomplete Paraplegia,家居改善 Home modification,公共交通工具 Transportation,香港現有的服務Current Services in Hong Kong,幾乎所有的脊髓復康服務均由醫院管理局提供 Nearly all spinal cord rehabilitation are provided by HA三間由醫管局提供的脊髓復康醫院 3 SCI units unde
10、r the Hospital Authority香港區：麥理浩復康院, MacLehose Rehabilitation Centre 九龍區：九龍醫院, Kowloon Hospital新界區：大埔醫院, Tai Po Hospital高技術水準的設備 - FES, 矯具等State-of- the-art facilitiesFES, orthosis, etc,脊髓損傷的治療及再生的可能Potential for spinal cord repair and regeneration,再生療法Regenerative therapies,脊髓損傷研究的重要性 Importance of
11、Spinal Cord Injury (SCI) Research,研究脊髓損傷的病理組織學 To investigate pathohistology of Spinal Cord Injury：,甚麼因素阻止了脊髓損傷後軸突的再生？ What stop axonal regeneration in Spinal Cord Injury?,如何促進脊髓損傷受損神經元的存活和再生？ How to enhance survival and regeneration of injured neurons in Spinal Cord Injury?,這些問題的答案將會給脊髓損傷病人提供新的療法。
12、Answer to these questions will contribute significantly for the new treatment methods for Spinal Cord Injury patients.,損傷後神經元如何、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的幹細胞、施萬細胞以及Oefactory Ensheathing Cells 細胞(OEC - 嗅鞘上皮細胞)移植等治療方法的機制。To confirm and prove mechanisms of treatment me
13、thods that have been used in clinical trial study for the Spinal Cord Injury patients, such as stem cell, Schwanns cell and OEC cell (Oefactory Ensheathing Cells) transplantations.,為脊髓損傷新藥的檢測提供動物模型。To provide animal models for testing effects of new drugs for Spinal Cord Injury.,Neuroscience Explori
14、ng the Brain, Second Edition.Bear MF, Connors BW, Paradiso MA,脊髓的主要功能（Main Functions of the Spinal Cord）,將感覺訊息從外周傳向腦，運動訊息從腦傳向外周。,構成局部回路和反射。 To perform locomotion and reflex.,To convey sensory impulses from periphery to the brain and to convey motor impulses from the brain to the periphery.,神經细胞死亡 （N
15、euronal cell death） a. 原發損傷 Primary injury (空洞cavity) b. 繼發損傷 Secondary injury,脊髓損傷後有侍解決的問題,2. 軸突切斷（Axotomy）,3. 脱髓鞘（Demyelination）,4. 膠質癍痕（Glial scar）,5. 抑制性分子（Inhibit molecules , NI-35, NI-250）,6. 血液供應不良（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 Sp
16、inal Cord Injury）,1. 神經细胞死亡（Neuronal cell death）波尼松龍治療减少细胞死亡，利用嗅鞘上皮細胞或幹细胞移植替代死亡的细胞。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 (Harper, PNAS 2004).,2. 軸突切断（Axot
17、omy）的治療增强軸突切斷神經元的再生能力。Enhance regeneration ability of axotomized neurons (Pears Nature Medicine, 2004; Yick, J Neurotrauma, 2004).,脊髓损傷的突破性研究(二)（Breakthrough Studies on the Field of Spinal Cord Injury）,3. 去髓鞘（Demyelination）的治療通過施萬细胞移植重建髓鞘 。Rebuild myelination by Schwanns cell transplantation (Xu, EJ
18、N 1999; Sivasankaran, Nature Neurosci. 2004).,4,5,6. 膠質癍痕及抑制性分子（Glial scar and Inhibit molecules）通過改變局部化學環境减少癍痕形成，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胞,Clinical Trials Ce
19、ntreFaculty of MedicineThe University of Hong Kong,8/F Clinical Pathology BuildingQueen Mary Hospital, Hong KongTel: (852) 2855 4664Fax: (852) 2974 1248E-mail: ctcentrehkucc.hku.hkwww.hku.hk/ctc,香港大學醫學院臨床試驗中心,due to the lack of investigators and patients in the established regions.,Study sites,Drug
20、development has become a global activity,由於研究員及合適参與臨床試驗的病人在已發展地區均出現短缺，臨床試驗正趨向全球化。,試驗場地,19801990,1996,ICH GCP Guideline,良好臨床試驗管理規範,已發出之臨床試驗證書,Global clinical trialsInto China and HKfrom other regions吸引世界各地之科研機構到中、港進行臨床試驗,Our aim我們的目標,Products from China and HK協助中、港之醫藥產品進軍國際市場,Our aim我們的目標,Highly qual
21、ified clinical investigators 高質素之臨床研究員Scientific expertise 科學專業知識Experienced in clinical research 豐富之臨床研究經驗High population density 高人口密度Excellent infrastructure 優良之基建 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 出版數目 (1991-2002),Clinical Trial / Re
22、search Experience 臨床試驗/研究經驗,Hong Kong Hospital Authority Clusters,HA,7 Clusters七個聯網43 Hospitals/Institutions四十三間醫院/機構29,022 Beds二萬九千零二十二個床位6.8 Million Population六百八十萬人口,香港醫院管理局聯網,Hong Kong Hospital Authority Clusters,Compliance with ICH GCP 符合良好臨床試驗管理規範之標準Uniform operations 統一運作標準HA Guidelines 醫院管理局
23、指引SOPs 標準運作程序Trained EC members 曾受訓之倫理委員會會員,Ethics Committees 倫理委員會,香港醫院管理局聯網,Established in 1998 under the Faculty of Medicine of The University of Hong Kong (founded in 1887)於一九九八年在香港大學醫學院之下成立The first full-service Academic Research Organization (ARO) in clinical trials in Asia亞洲首間一站式臨床試驗學術研究機構,Cl
24、inical Trials Centre 臨床試驗中心,Objective: To offer one-stop solutions to clinical trial sponsors and investigators,目標: 提供一站式服務予臨床試驗贊助商及研究員,Organization Structure 組織架構,Sponsors with a Master Clinical Trial Contract with HKU部份已與香港大學訂定標準合約之贊助商,Services 服務,Clinical Trials 臨床試驗,CTC No. of Sponsored Trials C
25、ontracted Per Year受贊助之臨床試驗總數(每年),Types of Trials by Therapeutic Area按專科分類,Types of Trials by Trial Phase按臨床試驗期分類,Type of clinical trials 臨床試驗之種類,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,內分泌及新陳代謝科,三期,四期,其他,二期,精神科,5 clinical laboratories:Anatomical PathologyClinical BiochemistryClini
26、cal ImmunologyHaematologyMicrobiology五大臨床實驗室：組織及細胞病理臨床生化臨床免疫血液微生物學Fully accredited by the College of American Pathologists (CAP) (under the category of large multidiscipline laboratory),Laboratory Facilities 實驗室設備,得到美國病理學家學會(CAP)之認証(隸屬大型多功能實驗室組別),Master of Medical Sciences / PgDip / PgCert 醫療科學碩士/研究
27、院文憑/研究院證書- Clinical Trials Research Methodology 臨床試驗研究方法學- Medical Statistics 統計分析GCP courses 良好臨床試驗管理規範課程EC members training倫理委員會會員之培訓Symposia / International conferences講座/國際會議Web-based Investigators Certification Programme研究員網上訓練課程,Educational Activities 教育活動,Pre-study activities試驗前,Study activit
28、ies試驗中,On the conduct of Clinical Trials臨床試驗程序,Post-study activities試驗後,Protocol CRFsInvestigatorTrainingGMPFinanceApprovalsInsuranceLogistics,Spinal Cord I. Research脊骨創傷研究,試驗方案,研究者培訓,藥品生產質量管理規範,財務,病例報告表,保險,物流,批核,Pre-study activities試驗前,Study activities試驗中,Post-study activities試驗後,Site activitiesPro
29、ject Manag.(QA)Data Manag.Safety Monitoring,研究單位活動,安全監控,項目管理(品質保証),數據處理,On the conduct of Clinical Trials臨床試驗程序,Spinal Cord I. Research脊骨創傷研究,Pre-study activities試驗前,Study activities試驗中,Post-study activities試驗後,Data Manag.Medical StatisticsMedical WritingReporting,醫學報告撰寫,報告,數據處理,統計分析,On the conduct of Clinical Trials臨床試驗程序,Spinal Cord I. Research脊骨創傷研究,
