肖传国和肖式反射弧科普文# WaterWorld - 未名水世界
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你们看看: 比较长,
转一篇文章。让事实为肖传国说话
转自:虹桥科教论坛 http://www.rainbowplan.org/bbs/topic.php?topic=114563&select=&forum=1
有人在散仙谷转了一篇文章。应该把这篇文章广为转发。让当局和国内不明真相的人民
都知道肖传国的医学探索的价值。方舟子夹私打假必然会被钉在科学的耻辱柱上。
“肖氏反射弧”真相解析
肖传国教授在世界上第一个提出并证实 “人工建立体神经-内脏神经反射弧” 用于治
疗各种脊髓损伤导致的排尿障碍。这一发现在肖传国与方舟子之间挑起了一场科学与反
科学长达五年的论战。为帮助公众了解这场论战的事实真相,本文首先从学术角度根据
科学文献和科学事实对“肖氏反射弧”作一番解析。
反射是神经支配机体生理机能的基本方式。反射弧一般由感受器,传入神经,反射中枢
,传出神经和效应器组成。正常的排尿反射由位于脑干和大脑皮层的高级排尿中枢控制
达骶髓的排尿反射初级中枢完成。膀胱充盈时,膀胱壁的牵张感受器受到刺激而兴奋。
冲动传入高级中枢产生排尿欲。中枢经过判断认为可以排尿,于是发出神经冲动沿下行
传导束到脊髓初级排尿中枢,然后由副交感神经元发出发出神经冲动导致膀胱逼尿肌肌
收缩,同时尿道括约肌放松,尿便经尿道口排出。中枢神经系统(从头部到骶髓)损伤
的早期可导致逼尿肌无反射和尿道扩约肌张力的提高。膀胱失去随意排尿的能力。
“肖氏反射弧”是媒体炒作生成的名词。肖传国的论文使用的术语是“体神经—自主神
经反射弧”或者“皮肤-中枢神经-膀胱反射通道”。“皮肤-中枢神经-膀胱反射通道”
是由手术建立的人造神经反射。目的是治疗因脊髓损伤导致的排尿障碍。具体方法是切
断左侧腰5前角神经根并将其与控制膀胱逼尿肌的骶2或/和骶3前角神经根吻合。保持腰
5后角神经根完整无损。通过刺激腰5相应的皮肤区,神经冲动从腰5后角神经根传入。
激发腰5前角神经元发出动作电位,由腰5前角神经根传到膀胱引起逼尿肌收缩,到达可
控排尿的目的。
这一构想的实验研究必须证明以下几个问题。第一,左侧腰5前角神经根与控制膀胱逼
尿肌的骶2或/和骶3前角神经根吻合后,神经是否能够再生。通过神经切片电镜和显微
镜观察,可以证明神经吻合后是死的还是活的。第二,再生的神经是否能对膀胱逼尿肌
形成支配。通过神经纤维酶示踪观察可以证明吻合后的神经是否可以传递神经介质。第
三,吻合后的腰5前角神经,在皮肤感觉冲动传入脊髓腰5后角时,是否能向膀胱释放动
作电位。通过神经电生理记录可以得到确认。第四,腰5前角神经冲动到达膀胱时,是
否可以激发逼尿肌收缩。通过膀胱内压力测定可以证明。以上每一步实验必须得到重复
实验证明。
通过本人复习肖传国从1999年到2006年在中国期刊和英文国际期刊的论文,毫无疑问,
肖传国通过上述的实验证明了他的构想是可行的。这些论文发表的期刊均属泌尿外科顶
级期刊。论文的引用少的有20次,多的达70次。本人没有查到否定肖传国以上实验结果
的论文。发现有两个中国作者发表了与肖传国相同的结果。根据上述事实,肖传国第一
个提出并证明的“皮肤-中枢神经-膀胱反射通道”在实验室条件下是一个可以重复证实
的客观存在。到目前为止,没有看到任何学者通过正式的学术交流媒介对此提出反对意
见。(附录1,肖传国论文部分目录)
但是,在大众传播媒介,我们可以看到有的专家学者发表不同的观点。北京大学泌尿外
科研究所名誉所长、中国泌尿外科学唯一的中国工程院院士郭应禄表示“肖传国的这个
手术在道理上能讲得通,但不是所有病人的神经都能接得上的而且你得能找得到神经才
能接”,郭应禄说,“所以,就算他说得对,能起作用也是有限制的。”武警总医院病
理科主任纪小龙也表示,神经愈合至今仍是医学上的一个难题,“神经是很难长在一起
的。打个比方,每根神经就像电话线,里面有好多分支,只有每一根分支都对上了,它
才能长好。而现有的任何显微手术都做不到这点,只能靠两根神经自己去找,手术能否
成功存在偶然因素。“我是专门研究神经再生的,我认为这种想法根本就是无稽之谈。
”中日友好医院神经外科主任于炎冰告诉《北京科技报》,“肖式反射弧”技术原理就
是让重新连接后的中枢神经再生,但是想要使中枢神经再生基本上没有可能。因为一个
器官它是由很多条神经共同支配的,如何寻找到与器官控制相对应的神经其实非常困难
,如果接错或破坏了原有的神经,手术后的结果可能会导致想恢复的功能没有恢复,而
原来的功能也会受到影响。
Nile根据肖传国的实验结果结合已经得到广泛接受的医学理论对以上的观点分析如下。
以上引述三位专家的意见可以归结为两个问题。第一个问题,手术后神经能否再生,能
否长在一起。肖式反射弧”技术原理就是让重新连接后的中枢神经再生,但是想要使中
枢神经再生基本上没有可能。Nile可以肯定中日友好医院神经外科主任于炎冰没有看过
肖传国的论文,不了解“皮肤-中枢神经-膀胱反射通道”的具体手术方法。具体手术方
法是切断左侧腰5前角神经根并将其与控制膀胱逼尿肌的骶2或/和骶3前角神经根吻合。
根据神经科学的基本理论,脊髓神经根不是中枢神经,是外周神经。手术对脊髓中的中
枢神经不造成任何损害。中枢神经损伤后不可能再生。但是,外周神经损伤后是可以再
生的。如果外周神经损伤后不可再生,那么所有的断肢再植手术都不可能成功。如果有
人对这个问题有疑问,请参阅附录2中枢神经外周神经的定义和神经再生的理论。另外
,神经吻合后,理论上可以再生,而实际上究竟是否能成功再生,是否每次手术都可以
成功再生。这是一个完全可以通过实验操作来回答的问题。根据肖传国和其他作者的实
验结果。吻合后神经的再生是一个可以不断反复验证的科学事实。
第二个问题。神经吻合会不会把神经接错。神经吻合的确有把神经接错的问题。可以把
传出的运动神经与传入的感觉神经错接。但是,把腰5前角神经与骶2,3前角神经吻合
不可能发生上述的错误。第一,所有的前角神经都没有任何感觉神经纤维成分。因此把
腰5前角神经与骶2,3前角神经吻合不可能出现错把感觉与运动神经对接的问题。第二
,腰5前角神经根由躯体运动神经纤维组成,而骶2,3前角神经根包含副交感和躯体运
动神经。肖传国的基本构想就是用躯体运动神经代替原有的副交感神经来人工造成膀胱
收缩。因此这个手术的另一个名称就是“体神经—自主神经反射弧” (somatic-
central nervous system-autonomic reflex pathway)这里的自主神经既副交感神经
。因此用运动神经与副交感神经吻合是治疗的手段,也不存在神经错接的问题。
“皮肤-中枢神经-膀胱反射通道”的根本目的是治疗脊髓损伤导致的排尿障碍。这一方
法用于临床疗效究竟如何,是这一发现究竟有没有医学价值的关键问题。把一种探索性
的手术方法用于临床治疗,本身就面临一个从动物到人的沟壑。动物神经组织的再生速
度比人快。动物实验可以人为设定实验初始条件,而病人的病情可以千差万别。动物实
验可以有一致的标准判断成功还是失败,而病人很难用同一个标准判断有效无效。动物
实验不需要考虑手术的副作用,而在人身上,很可能副作用带来的损害超过疗效带来的
利益。因此任何一种治疗的疗效评定都必须将上述的条件考虑在内科学地建立评定标准。
对于反射弧手术的疗效评定,从有关论文来看,比较一致的标准是:1.恢复自主排尿的
程度;2. 尿流动力学指标的改善;3. 能否不依赖导尿管。如果以完全恢复自主排尿为
有效。那么这个手术的疗效很可能就是零。如果仅仅以尿流动力学指标改善为有效,疗
效很可能就接近100%。从1995年到2010年,肖传国进行反射弧手术2000例。在最大的一
个样本是1500例患者中的500例得到随访,有效率85%。学术界引用的是肖传国本人在国
际专业期刊的两个大宗病例报道:92例脊髓损伤患者88%术后一年达到可控排尿和110例
脊髓膨出患儿87%在术后一年可以成功完成可控排尿。
而坚持指控肖传国是学术骗子的方舟子们对手术的有效率进行了山寨调查。根据发表在
新语丝的一篇题为《肖氏手术”治愈率:85%,还是0%?》,可以看到他们调查的结果
:“2009年9月,当资金较为充裕之时,调查取证的工作再次启动。这一次,据患者彼
此通信获得的150多人中,打通电话的有80多人,现场寻访人数15人。彭剑说,目前数
字还在不断增加,每天至少有2个,多至三四个电话打过来为案件提供佐证。在迄今为
止所接触过的接受了肖氏手术的病友中,调查结果显示没有一例完全成功,手术有明显
效果的比率也很低——这与医院方面所宣传的“治愈率85%”形成鲜明对照。”
以上的文字用正式的疗效评估语言可以作这样的解读:本寨以电话和现场采访的方式对
95名反射弧术后患者进行了调查。结果表明,手术完全成功率为零。明显有效率不祥。
调查过程采用的问卷不予公布。这一调查结果与85%的“治愈率”的确是有天壤之别。
但是与肖传国在专业文献中报道的87%-88%的有效率没有任何矛盾。
任何治疗方法都有副作用,反射弧手术的主要副作用就是下肢运动功能受损。这个问题
对完全截瘫病人没有影响,但是对本来保留有一定程度的下肢运动功能的脊髓膨出患儿
就是一个问题。这一副作用完全在医生和患者的预料之中,因为是该手术用本来是负责
下肢运动的神经去支配膀胱排尿,不可能不影响左下肢的运动。对此,肖传国已经对手
术方法进行了改良。把原来用全部左侧腰5前角神经根改为用1/3到一半的神经根,这一
改良减轻了对下肢运动的副作用。
美国William Beaumont医院泌尿外科主任Kenneth M. Peters 2010年4月在《当代膀胱
功能紊乱报道》杂志发表文章,对肖传国发现的反射弧手术方法予以综述:(附录3)
Dr. C. G. Xiao from China was the first to popularize bladder reinnervation
through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This
concept has gained international attention, and attempts to create other
somatic-to-autonomic reflex arcs to assist with voluntary voiding have been
studied. In this review, we discuss the current state of the literature in
this new field.
2010年8月Peters与同行们在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结果
:(附录4)
Results
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle groups at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
Conclusions
At 1 year a novel reflex arc with stimulation of the appropriate dermatome
was seen in the majority of subjects. Improvements in voiding and bowel
function were noted. Lower extremity weakness was mostly self-limited,
except in 1 subject with a persistent foot drop. More patients and longer
followup are needed to assess the risk/benefit ratio of this novel procedure.
两位该杂志编辑对这篇论文发表了评论,认为这9例手术的结果与肖传国作的110例87%
有效率不同,缺乏对照,没有统计学意义(附录5)。同时刊载了论文作者Peter等人对
编辑的评论做出了回应。Peter等人认为,发表这9例一年随访结果的目的是证明皮肤到
膀胱反射弧是可以实现的,同时也应该了解到手术可能带来的副作用,并以此唤起全美
医学界对这项研究的注意,加强对这种手术研究。William Beaumont医院泌尿外科2009
年底得到美国卫生研究所NIH 230万美元研究基金,由Beaumont医院牵头,在美国几个
主要医学院多中心推广研究反射弧手术(附录6)。
从肖传国1999年在美国得到NIH RO1基金64万开展反射弧手术实验室研究到William
Beaumont医院泌尿外科2009年得到美国卫生研究所NIH RO1 基金230万美元,十年中肖
传国发现的“皮肤-中枢神经-膀胱反射通道”已经产生了近百篇论文,2000余例有效率
80%以上的手术,并两度写入外科学教科书。肖传国的反射弧手术从他一个人单枪匹马
的实验室研究发展到美国多家医院共同参与的临床应用研究。就在他因雇凶打人下狱前
的一周,还在阿根廷讲学并实施了8例示范手术。
方舟子2005年发表《脚踏两只船的院士候选人》。文章列举四项证据证明肖传国是学术
骗子。1.在美国担任全职工作。2. 在国际期刊上发表的文章只有4篇。3. 从来没有得
到美国泌尿学会奖。4. 用“肖氏手术”在网上只找到一个结果。武汉两级法院根据肖
传国提供的证据判决方舟子捏造证据诽谤他人罪名成立。北京两级法院驳回肖传国对方
舟子的诉讼根据的不是他们经过研判认定方舟子的证据确实可信,而是他们强行把上述
证据界定为“学术争论”而拒绝法律干预。
事实上,在所有打击肖传国的“肖氏反射弧”是学术造假的文章中,方舟子集团从来没
有是根据医学理论,学术文献,或者他们自己的研究结果对肖传国的工作进行学术质疑
。方舟子最近发表了一篇文章《美国泌尿学杂志质疑“肖氏手术”》又是一次偷梁换柱
,本末倒置的拙劣表演。美国泌尿学杂志2010年8月发表的Peter等人的论文证明反射弧
手术后一年,大多数病人的自主排尿能力有了改善,而手术导致的下肢无力是有限的。
论文同时也认为需要更长时间的随访来评价疗效。真正质疑肖氏手术的不是这篇论文,
而是杂志编辑对该论文的评论。而且原文作者Peter等人对编辑的质疑也作出了恰如其
分的回应。但是,事实到了方舟子手里就面目全非。方舟子刻意突出杂志编辑对原始论
文的负面评价,并附上了全文。可是论文最重要的部分,原始论文本身的结果和结论居
然在他的文章中完全失踪了。很明显,文章的结果和结论是方舟子们最不愿意看到的。
而他们最不愿意看到的部分恰恰是最原始的科学事实。
学术争论,学术打假应该运用科学理论以及研究结果辨别学术问题本身的真伪。避开学
术问题本身而对研究者进行人格攻击,这种行为与科学问题没有任何关系。学术争论,
学术打假也必需同行的监督与评议,以文献的方式发表在正式的学术平台,决不可以通
过大众媒体来进行,因为大众传媒没有辨别科学问题正确与谬误的能力。中国学术界人
士应该自觉地把自己的言论置于同行的学术监督之下,拒绝在学术平台之外,发表对他
人学术成果的评价。对于这些在科学的幌子下用谎言任意诽谤他人的骗子们,打击他们
最有效的手段就是用事实说明真相。是骗子一定害怕事实,隐瞒事实,歪曲事实,甚至
伪造事实。但是,事实就像阳光,谁也休想垄断。
附录1:肖传国论文部分目录
“SKIN-CNS-BLADDER” REFLEX PATHWAY FOR MICTURITION AFTER SPINAL CORD INJURY
AND ITS UNDERLYING MECHANISMS
CGUO XIAO, WC DE GROAT, CJ GODEC, C DAI, … - The Journal of …, 1999 -
Elsevier
A detrusor contraction was initiated at short latency by scratching the skin
or by percutaneous
electrical stimulation in the L7 dermatome. Maximal bladder pressures during
this stimulation
were similar to those activated by bladder distension in control animals. ...
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An artificial somatic-central nervous system-autonomic reflex pathway for
controllable micturition after spinal cord injury: preliminary results in 15
patients
CG Xiao, MX Du, C Dai, B Li, VW Nitti, WC de … - The Journal of …, 2003 -
Elsevier
... Fig. 1. Skin-CNS-bladder reflex pathway. View Within Article. ... Test
of skin-CNS-bladder reflex
by scratching L5 dermatome caused immediate response of detrusor and
external urethral
sphincter but voiding was not yet synergic and bladder emptying was
incomplete. ...
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Reinnervation for neurogenic bladder: historic review and introduction of a
somatic-autonomic reflex pathway procedure for patients with spinal cord
injury or spina …
CG Xiao - European urology, 2006 - Elsevier
... related skin. A new concept may be derived from the skin-CNS-bladder
reflex pathway:
the impulses delivered from the efferent neurons of a somatic reflex arc can
be
transferred to initiate responses of an autonomic effector [22]. ...
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An artificial somatic-autonomic reflex pathway procedure for bladder control
in children with spina bifida
CG Xiao, MX Du, B Li, Z Liu, M Chen, ZH Chen, P … - The Journal of …, 2005
- Elsevier
... through the S2, S3 or S4 VR. The efferent impulses of the skin-CNS-
bladder reflex
pass through the pudendal nerve and should activate the external sphincter
before
the bladder. Therefore, activation of bladder muscle will be ...
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[PDF] 体神经 2 内脏神经吻合后神经纤维再生过程的光镜电镜观察
zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2002 - 88889595.
zhengdasifuyuan.com
基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出
青年人才基金资助项目(39925033) 作者单位:430022 武汉,华中科技大学同济医学院附
属协和医院泌
尿外科 ... Light microscope and electron microscope study of nerve
regenerated ...
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[PDF] 人工体神经 2 内脏神经反射弧传出通路神经追踪研究
zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2003 - 88889595.
zhengdasifuyuan.com
基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出 青年人才基金项目(
39925033)
作者单位:430022 武汉,华中科技大学同济医学院附属协和医院泌 尿外科 ... Neural
tracing study
of efferent pathway of the artificial somatic2autonomic reflex arc XIAO
Chuan2guo ,LI ...
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SKIN-CNS-BLADDER REFLEX ARC FOR MICTURITION AFTER SCI
Chuan-guo Xiao
New York University School Of Medicine New York, Ny 10016
Grant 5R01DK053063-05 from National Institute Of Diabetes And Digestive And
Kidney Diseases IRG: ZRG1
Abstract: The neurological bladder caused by spinal cord injury (SCI)
presents a significant medical and social problem. There is no satisfactory
treatment yet. Supported by the Paralyzed Veterans of America and NIH, a new
reflex pathway, \\\\\\\"Skin-CNS-Bladder\\\\\\\" for controlled micturition
after SCI has been successfully established in rat, cat and canine models.
Preliminary clinical application of 14 SCI patients also provided very
promising results. The study proposed here is to transfer the Skin-CNS-
Bladder reflex functions. The ventral root (VR) of a lumbar nerve (L5) below
the spinal cord lesion will be anastomosed to the sacral VR (S2 and/or S3)
which innervate the bladder, while leaving the intact L5 dorsal root (DR) as
a started of micturition. After the axonal regeneration, controllable
voiding would be initiated by scratching the L4 dermatome. Effect of the new
reflex pathway on bladder function will be evaluated by means of
electrophysiology and urodynamics. Its effect on bowel and sexual functions
will also be studied. The procedure may revolutionize the treatment of
neurogenic bladder after SCI, It requires relatively minor surgery on 2
paralyzed nerves. It does not involve implantation of electrodes or other
devices but provides unique voluntary control of bladder emptying.
Scientifically, the study will further prove the new concept derived from
the unique somatic-autonomic reflex that the impulses delivered from the
efferent neurons of a somatic reflex arc may be transferred to initiate
response of an autonomic effector. This new concept may be widely useful,
not only for neurogenic bladder, but also for other problems caused by the
spinal cord injury or diseases.
Keywords: electrophysiology, human therapy evaluation, neurogenic urinary
bladder disorder, neuroregulation, neurosurgery, somatic reflex, spinal cord
injury, urination, central nervous system, clinical trial, functional
ability, outcomes research, quality of life, skin, urinary electronic
stimulator, clinical research, human subject
Project start date: 1999-09-30
Project end date: 2007-12-31
5R01DK053063-05 (2004): $642796
附录2:中枢神经外周神经的定义和神经再生的理论
The peripheral nervous system, or PNS, consists of the nerves and ganglia
outside of the brain and the spinal cord.[1] The main function of the PNS is
to connect the central nervous system (CNS) to the limbs and organs. Unlike
the CNS, the PNS is not protected by the bone of spine and skull, or by the
blood-brain barrier, leaving it exposed to toxins and mechanical injuries.
The peripheral nervous system is divided into the somatic nervous system and
the autonomic nervous system; some textbooks also include sensory systems.[
2]
Neuroregeneration in the PNS occurs to a significant degree.[5] Axonal
sprouts form at the proximal stump and grow until they enter the distal
stump. The growth of the sprouts are governed by chemotactic factors
secreted from Schwann cells.
Injury to the peripheral nervous system immediately elicits the migration of
phagocytic cells, Schwann cells, and macrophages to the lesion site in
order to clear away debris such as damaged tissue. When a nerve axon is
severed, the end still attached to the cell body is labeled the proximal
segment, while the other end is called the distal segment. After injury, the
proximal end swells and experiences some retrograde degeneration, but once
the debris is cleared, it begins to sprout axons and the presence of growth
cones can be detected. The proximal axons are able to regrow as long as the
cell body is intact, and they have made contact with the neurolemmocytes in
the endoneurial channel. Human axon growth rates can reach 2 mm/day in small
nerves and 5 mm/day in large nerves.[4] The distal segment, however,
experiences Wallerian degeneration within hours of the injury; the axons and
myelin degenerate, but the endoneurium remains. In the later stages of
regeneration the remaining endoneurial tube directs axon growth back to the
correct targets. During Wallerian degeneration, Schwann cells grow in
ordered columns along the endoneurial tube, creating a band of Bungner (boB)
that protects and preserves the endoneurial channel. Also, macrophages and
Schwann cells release neurotrophic factors that enhance re-growth.
Unlike peripheral nervous system injury, injury to the central nervous
system is not followed by extensive regeneration.
附录3:美国William Beaumont医院泌尿外科主任Kenneth M. Peters对肖传国发现的反
射弧手术方法予以综述
Bladder Reinnervation: Is it Becoming a Reality?
Don Bui, Kevin Feber and Kenneth M. Peters
Abstract
Management of neurogenic voiding dysfunction presents a clinical challenge.
Traditional therapies such as clean intermittent catheterization and
antimuscarinics have saved countless lives. However, a desire remains to
normalize the voiding in patients suffering from spinal cord injuries.
Bladder reinnervation is a novel surgical technique that shows promise in
helping those with spinal cord-related neurogenic voiding dysfunction. Dr. C
. G. Xiao from China was the first to popularize bladder reinnervation
through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This
concept has gained international attention, and attempts to create other
somatic-to-autonomic reflex arcs to assist with voluntary voiding have been
studied. In this review, we discuss the current state of the literature in
this new field.
Keywords Neurogenic bladder - Nerve transfer - Incontinence - Spina bifida -
Spinal cord injury
Current Bladder Dysfunction Reports Volume 5, Number 2, 59-62,
附录4:Kenneth M. Peters在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结
果:
THE JOURNAL OF UROLOGY, Vol. 184, 702-708, August 2010
Outcomes of Lumbar to Sacral Nerve Rerouting for Spina Bifida
Kenneth M. Petersa, Benjamin Girdlera, Cindy Turzewskia, Gary Trockc, Kevin
Febera, William Nantaub, Brian Bushb, Jose Gonzaleza, Evan Kassa, Juan de
Benitoa, Ananias Dioknoa
Received 25 November 2009 published online 21 June 2010.
Purpose
Restoring bladder and bowel function in spina bifida by creation of a skin-
central nervous system-bladder reflex arc via lumbar to sacral nerve
rerouting has a reported success rate of 87% in China. We report 1-year
results of the first North American trial on nerve rerouting.
Materials and Methods
Nine subjects were enrolled in the study. Intradural lumbar to sacral nerve
rerouting was performed. Subjects underwent urodynamic testing with
stimulation of the cutaneous dermatome and careful neurological followup.
Adverse events were closely monitored along with changes in bowel and
bladder function.
Results
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle groups at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
Conclusions
At 1 year a novel reflex arc with stimulation of the appropriate dermatome
was seen in the majority of subjects. Improvements in voiding and bowel
function were noted. Lower extremity weakness was mostly self-limited,
except in 1 subject with a persistent foot drop. More patients and longer
followup are needed to assess the risk/benefit ratio of this novel procedure.
Key Words: nerve transfer, spina bifida cystica, spina bifida occulta,
urinary bladder, neurogenic
Abbreviations and Acronyms: DR, dorsal root, EMG, electromyography, VR,
ventral root
http://www.jurology.com/article/S0022-5347(10)03053-3/abstract
附录5:对Kenneth M. Peters论文杂志编辑的评论和论文作者Peter等的回应
EDITORIAL COMMENTS
The Beaumont Hospital in Michigan is one of the first American institutes
that took up clinical trials of the controversial Xiao Procedure. We have
previously questioned their clinical outcomes and their misleading
propaganda in our Open Letter of Complaint against the Xiao Procedure.
More recently, the hospital has also become the first institute to publish
clinical results of Xiao Procedure in an established scientific journal. Dr.
Kenneth Peters and his coauthors wrote in the Journal of Urology of their
results:
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle group at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
The authors present the first North American experience with lumbar to
sacral nerve rerouting for patients with spina bifida. The results from this
study and previous animal and clinical studies by Xiao clearly demonstrate
that nerve rerouting produces a somatic-autonomic or cutaneous/bladder
reflex with stimulation of the lower extremity dermatome. What is also clear
is that the clinical benefit of the procedure is not at all similar to
previous reports.
Although the authors did an excellent job of following the patients and
characterizing their changes, the results are hard to validate without a
control population going through the same rigorous surveillance regimen. In
particular the improved bowel continence and minimal changes in bladder
compliance may not be statistically significant. The fact that most patients
were still on clean intermittent catheterization and none achieved complete
urinary continence is troubling in light of the report of 87% success with
110 children with spina bifida presented by Xiao. One has to wonder if most
of these children are not voiding volitionally or using the newly developed
cutaneous reflex, and how much reinnervation has a role in this surgery. Is
it possible that unilateral denervation of the S3 ventral motor nerve
produced improved compliance and continence, as previously reported in
numerous clinical series?
I congratulate the authors for taking on this challenge. I hope this study
leads to a rebirth or refocus regarding neurosurgical treatments of
neuropathic bowel and bladder. I strongly agree with the authors that this
procedure should remain on a research protocol only.
Eric A. Kurzrock
Pediatric Urology
U. C. Davis Children’s Hospital
Sacramento, California
One of the most curious findings is the discrepancy between urodynamic data
and subjective voiding. One patient exhibited a decrease in capacity and an
absence of reflex arc, and yet he subjectively reported improved bladder and
bowel function! I could not help but speculate that his voiding after the
procedure could simply be the bladder emptying via intra-abdominal pressure
generation against an open bladder neck, given his preoperative stress
incontinence. Xiao reported that more than 87% of 110 patients gained
sensation and continence within 1 year (reference 7 in article). In
comparison, the current patients undergoing the identical procedure with the
help of Xiao himself only showed a modest improvement in objective
urodynamic studies and subjective reporting. Unless the innovators provide a
sound argument and data for the validity of the procedure, there is a great
danger of its improper and rapid adaptation by patients and the medical
community at large.
John M. Park
Department of Urology
University of Michigan Medical School
Ann Arbor, Michigan
REPLY BY AUTHORS
We agree this is a challenging study on many levels. The intent of
publishing these 1-year data was to understand the potential complications
associated with lumbar to sacral nerve rerouting, demonstrate that a
cutaneous to bladder reflex is achievable and, given the nationwide interest
in this procedure, reinforce the need to continue this rigorous research
protocol until more is known about the risk-benefit profile. Hopefully our
36-month data will shed more light on the clinical usefulness of this
innovative procedure.
附录6:William Beaumont医院泌尿外科2009年底得到美国卫生研究所NIH 230万美元研
究基金
http://projectreporter.nih.gov/project_info_description.cfm?aid
转一篇文章。让事实为肖传国说话
转自:虹桥科教论坛 http://www.rainbowplan.org/bbs/topic.php?topic=114563&select=&forum=1
有人在散仙谷转了一篇文章。应该把这篇文章广为转发。让当局和国内不明真相的人民
都知道肖传国的医学探索的价值。方舟子夹私打假必然会被钉在科学的耻辱柱上。
“肖氏反射弧”真相解析
肖传国教授在世界上第一个提出并证实 “人工建立体神经-内脏神经反射弧” 用于治
疗各种脊髓损伤导致的排尿障碍。这一发现在肖传国与方舟子之间挑起了一场科学与反
科学长达五年的论战。为帮助公众了解这场论战的事实真相,本文首先从学术角度根据
科学文献和科学事实对“肖氏反射弧”作一番解析。
反射是神经支配机体生理机能的基本方式。反射弧一般由感受器,传入神经,反射中枢
,传出神经和效应器组成。正常的排尿反射由位于脑干和大脑皮层的高级排尿中枢控制
达骶髓的排尿反射初级中枢完成。膀胱充盈时,膀胱壁的牵张感受器受到刺激而兴奋。
冲动传入高级中枢产生排尿欲。中枢经过判断认为可以排尿,于是发出神经冲动沿下行
传导束到脊髓初级排尿中枢,然后由副交感神经元发出发出神经冲动导致膀胱逼尿肌肌
收缩,同时尿道括约肌放松,尿便经尿道口排出。中枢神经系统(从头部到骶髓)损伤
的早期可导致逼尿肌无反射和尿道扩约肌张力的提高。膀胱失去随意排尿的能力。
“肖氏反射弧”是媒体炒作生成的名词。肖传国的论文使用的术语是“体神经—自主神
经反射弧”或者“皮肤-中枢神经-膀胱反射通道”。“皮肤-中枢神经-膀胱反射通道”
是由手术建立的人造神经反射。目的是治疗因脊髓损伤导致的排尿障碍。具体方法是切
断左侧腰5前角神经根并将其与控制膀胱逼尿肌的骶2或/和骶3前角神经根吻合。保持腰
5后角神经根完整无损。通过刺激腰5相应的皮肤区,神经冲动从腰5后角神经根传入。
激发腰5前角神经元发出动作电位,由腰5前角神经根传到膀胱引起逼尿肌收缩,到达可
控排尿的目的。
这一构想的实验研究必须证明以下几个问题。第一,左侧腰5前角神经根与控制膀胱逼
尿肌的骶2或/和骶3前角神经根吻合后,神经是否能够再生。通过神经切片电镜和显微
镜观察,可以证明神经吻合后是死的还是活的。第二,再生的神经是否能对膀胱逼尿肌
形成支配。通过神经纤维酶示踪观察可以证明吻合后的神经是否可以传递神经介质。第
三,吻合后的腰5前角神经,在皮肤感觉冲动传入脊髓腰5后角时,是否能向膀胱释放动
作电位。通过神经电生理记录可以得到确认。第四,腰5前角神经冲动到达膀胱时,是
否可以激发逼尿肌收缩。通过膀胱内压力测定可以证明。以上每一步实验必须得到重复
实验证明。
通过本人复习肖传国从1999年到2006年在中国期刊和英文国际期刊的论文,毫无疑问,
肖传国通过上述的实验证明了他的构想是可行的。这些论文发表的期刊均属泌尿外科顶
级期刊。论文的引用少的有20次,多的达70次。本人没有查到否定肖传国以上实验结果
的论文。发现有两个中国作者发表了与肖传国相同的结果。根据上述事实,肖传国第一
个提出并证明的“皮肤-中枢神经-膀胱反射通道”在实验室条件下是一个可以重复证实
的客观存在。到目前为止,没有看到任何学者通过正式的学术交流媒介对此提出反对意
见。(附录1,肖传国论文部分目录)
但是,在大众传播媒介,我们可以看到有的专家学者发表不同的观点。北京大学泌尿外
科研究所名誉所长、中国泌尿外科学唯一的中国工程院院士郭应禄表示“肖传国的这个
手术在道理上能讲得通,但不是所有病人的神经都能接得上的而且你得能找得到神经才
能接”,郭应禄说,“所以,就算他说得对,能起作用也是有限制的。”武警总医院病
理科主任纪小龙也表示,神经愈合至今仍是医学上的一个难题,“神经是很难长在一起
的。打个比方,每根神经就像电话线,里面有好多分支,只有每一根分支都对上了,它
才能长好。而现有的任何显微手术都做不到这点,只能靠两根神经自己去找,手术能否
成功存在偶然因素。“我是专门研究神经再生的,我认为这种想法根本就是无稽之谈。
”中日友好医院神经外科主任于炎冰告诉《北京科技报》,“肖式反射弧”技术原理就
是让重新连接后的中枢神经再生,但是想要使中枢神经再生基本上没有可能。因为一个
器官它是由很多条神经共同支配的,如何寻找到与器官控制相对应的神经其实非常困难
,如果接错或破坏了原有的神经,手术后的结果可能会导致想恢复的功能没有恢复,而
原来的功能也会受到影响。
Nile根据肖传国的实验结果结合已经得到广泛接受的医学理论对以上的观点分析如下。
以上引述三位专家的意见可以归结为两个问题。第一个问题,手术后神经能否再生,能
否长在一起。肖式反射弧”技术原理就是让重新连接后的中枢神经再生,但是想要使中
枢神经再生基本上没有可能。Nile可以肯定中日友好医院神经外科主任于炎冰没有看过
肖传国的论文,不了解“皮肤-中枢神经-膀胱反射通道”的具体手术方法。具体手术方
法是切断左侧腰5前角神经根并将其与控制膀胱逼尿肌的骶2或/和骶3前角神经根吻合。
根据神经科学的基本理论,脊髓神经根不是中枢神经,是外周神经。手术对脊髓中的中
枢神经不造成任何损害。中枢神经损伤后不可能再生。但是,外周神经损伤后是可以再
生的。如果外周神经损伤后不可再生,那么所有的断肢再植手术都不可能成功。如果有
人对这个问题有疑问,请参阅附录2中枢神经外周神经的定义和神经再生的理论。另外
,神经吻合后,理论上可以再生,而实际上究竟是否能成功再生,是否每次手术都可以
成功再生。这是一个完全可以通过实验操作来回答的问题。根据肖传国和其他作者的实
验结果。吻合后神经的再生是一个可以不断反复验证的科学事实。
第二个问题。神经吻合会不会把神经接错。神经吻合的确有把神经接错的问题。可以把
传出的运动神经与传入的感觉神经错接。但是,把腰5前角神经与骶2,3前角神经吻合
不可能发生上述的错误。第一,所有的前角神经都没有任何感觉神经纤维成分。因此把
腰5前角神经与骶2,3前角神经吻合不可能出现错把感觉与运动神经对接的问题。第二
,腰5前角神经根由躯体运动神经纤维组成,而骶2,3前角神经根包含副交感和躯体运
动神经。肖传国的基本构想就是用躯体运动神经代替原有的副交感神经来人工造成膀胱
收缩。因此这个手术的另一个名称就是“体神经—自主神经反射弧” (somatic-
central nervous system-autonomic reflex pathway)这里的自主神经既副交感神经
。因此用运动神经与副交感神经吻合是治疗的手段,也不存在神经错接的问题。
“皮肤-中枢神经-膀胱反射通道”的根本目的是治疗脊髓损伤导致的排尿障碍。这一方
法用于临床疗效究竟如何,是这一发现究竟有没有医学价值的关键问题。把一种探索性
的手术方法用于临床治疗,本身就面临一个从动物到人的沟壑。动物神经组织的再生速
度比人快。动物实验可以人为设定实验初始条件,而病人的病情可以千差万别。动物实
验可以有一致的标准判断成功还是失败,而病人很难用同一个标准判断有效无效。动物
实验不需要考虑手术的副作用,而在人身上,很可能副作用带来的损害超过疗效带来的
利益。因此任何一种治疗的疗效评定都必须将上述的条件考虑在内科学地建立评定标准。
对于反射弧手术的疗效评定,从有关论文来看,比较一致的标准是:1.恢复自主排尿的
程度;2. 尿流动力学指标的改善;3. 能否不依赖导尿管。如果以完全恢复自主排尿为
有效。那么这个手术的疗效很可能就是零。如果仅仅以尿流动力学指标改善为有效,疗
效很可能就接近100%。从1995年到2010年,肖传国进行反射弧手术2000例。在最大的一
个样本是1500例患者中的500例得到随访,有效率85%。学术界引用的是肖传国本人在国
际专业期刊的两个大宗病例报道:92例脊髓损伤患者88%术后一年达到可控排尿和110例
脊髓膨出患儿87%在术后一年可以成功完成可控排尿。
而坚持指控肖传国是学术骗子的方舟子们对手术的有效率进行了山寨调查。根据发表在
新语丝的一篇题为《肖氏手术”治愈率:85%,还是0%?》,可以看到他们调查的结果
:“2009年9月,当资金较为充裕之时,调查取证的工作再次启动。这一次,据患者彼
此通信获得的150多人中,打通电话的有80多人,现场寻访人数15人。彭剑说,目前数
字还在不断增加,每天至少有2个,多至三四个电话打过来为案件提供佐证。在迄今为
止所接触过的接受了肖氏手术的病友中,调查结果显示没有一例完全成功,手术有明显
效果的比率也很低——这与医院方面所宣传的“治愈率85%”形成鲜明对照。”
以上的文字用正式的疗效评估语言可以作这样的解读:本寨以电话和现场采访的方式对
95名反射弧术后患者进行了调查。结果表明,手术完全成功率为零。明显有效率不祥。
调查过程采用的问卷不予公布。这一调查结果与85%的“治愈率”的确是有天壤之别。
但是与肖传国在专业文献中报道的87%-88%的有效率没有任何矛盾。
任何治疗方法都有副作用,反射弧手术的主要副作用就是下肢运动功能受损。这个问题
对完全截瘫病人没有影响,但是对本来保留有一定程度的下肢运动功能的脊髓膨出患儿
就是一个问题。这一副作用完全在医生和患者的预料之中,因为是该手术用本来是负责
下肢运动的神经去支配膀胱排尿,不可能不影响左下肢的运动。对此,肖传国已经对手
术方法进行了改良。把原来用全部左侧腰5前角神经根改为用1/3到一半的神经根,这一
改良减轻了对下肢运动的副作用。
美国William Beaumont医院泌尿外科主任Kenneth M. Peters 2010年4月在《当代膀胱
功能紊乱报道》杂志发表文章,对肖传国发现的反射弧手术方法予以综述:(附录3)
Dr. C. G. Xiao from China was the first to popularize bladder reinnervation
through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This
concept has gained international attention, and attempts to create other
somatic-to-autonomic reflex arcs to assist with voluntary voiding have been
studied. In this review, we discuss the current state of the literature in
this new field.
2010年8月Peters与同行们在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结果
:(附录4)
Results
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle groups at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
Conclusions
At 1 year a novel reflex arc with stimulation of the appropriate dermatome
was seen in the majority of subjects. Improvements in voiding and bowel
function were noted. Lower extremity weakness was mostly self-limited,
except in 1 subject with a persistent foot drop. More patients and longer
followup are needed to assess the risk/benefit ratio of this novel procedure.
两位该杂志编辑对这篇论文发表了评论,认为这9例手术的结果与肖传国作的110例87%
有效率不同,缺乏对照,没有统计学意义(附录5)。同时刊载了论文作者Peter等人对
编辑的评论做出了回应。Peter等人认为,发表这9例一年随访结果的目的是证明皮肤到
膀胱反射弧是可以实现的,同时也应该了解到手术可能带来的副作用,并以此唤起全美
医学界对这项研究的注意,加强对这种手术研究。William Beaumont医院泌尿外科2009
年底得到美国卫生研究所NIH 230万美元研究基金,由Beaumont医院牵头,在美国几个
主要医学院多中心推广研究反射弧手术(附录6)。
从肖传国1999年在美国得到NIH RO1基金64万开展反射弧手术实验室研究到William
Beaumont医院泌尿外科2009年得到美国卫生研究所NIH RO1 基金230万美元,十年中肖
传国发现的“皮肤-中枢神经-膀胱反射通道”已经产生了近百篇论文,2000余例有效率
80%以上的手术,并两度写入外科学教科书。肖传国的反射弧手术从他一个人单枪匹马
的实验室研究发展到美国多家医院共同参与的临床应用研究。就在他因雇凶打人下狱前
的一周,还在阿根廷讲学并实施了8例示范手术。
方舟子2005年发表《脚踏两只船的院士候选人》。文章列举四项证据证明肖传国是学术
骗子。1.在美国担任全职工作。2. 在国际期刊上发表的文章只有4篇。3. 从来没有得
到美国泌尿学会奖。4. 用“肖氏手术”在网上只找到一个结果。武汉两级法院根据肖
传国提供的证据判决方舟子捏造证据诽谤他人罪名成立。北京两级法院驳回肖传国对方
舟子的诉讼根据的不是他们经过研判认定方舟子的证据确实可信,而是他们强行把上述
证据界定为“学术争论”而拒绝法律干预。
事实上,在所有打击肖传国的“肖氏反射弧”是学术造假的文章中,方舟子集团从来没
有是根据医学理论,学术文献,或者他们自己的研究结果对肖传国的工作进行学术质疑
。方舟子最近发表了一篇文章《美国泌尿学杂志质疑“肖氏手术”》又是一次偷梁换柱
,本末倒置的拙劣表演。美国泌尿学杂志2010年8月发表的Peter等人的论文证明反射弧
手术后一年,大多数病人的自主排尿能力有了改善,而手术导致的下肢无力是有限的。
论文同时也认为需要更长时间的随访来评价疗效。真正质疑肖氏手术的不是这篇论文,
而是杂志编辑对该论文的评论。而且原文作者Peter等人对编辑的质疑也作出了恰如其
分的回应。但是,事实到了方舟子手里就面目全非。方舟子刻意突出杂志编辑对原始论
文的负面评价,并附上了全文。可是论文最重要的部分,原始论文本身的结果和结论居
然在他的文章中完全失踪了。很明显,文章的结果和结论是方舟子们最不愿意看到的。
而他们最不愿意看到的部分恰恰是最原始的科学事实。
学术争论,学术打假应该运用科学理论以及研究结果辨别学术问题本身的真伪。避开学
术问题本身而对研究者进行人格攻击,这种行为与科学问题没有任何关系。学术争论,
学术打假也必需同行的监督与评议,以文献的方式发表在正式的学术平台,决不可以通
过大众媒体来进行,因为大众传媒没有辨别科学问题正确与谬误的能力。中国学术界人
士应该自觉地把自己的言论置于同行的学术监督之下,拒绝在学术平台之外,发表对他
人学术成果的评价。对于这些在科学的幌子下用谎言任意诽谤他人的骗子们,打击他们
最有效的手段就是用事实说明真相。是骗子一定害怕事实,隐瞒事实,歪曲事实,甚至
伪造事实。但是,事实就像阳光,谁也休想垄断。
附录1:肖传国论文部分目录
“SKIN-CNS-BLADDER” REFLEX PATHWAY FOR MICTURITION AFTER SPINAL CORD INJURY
AND ITS UNDERLYING MECHANISMS
CGUO XIAO, WC DE GROAT, CJ GODEC, C DAI, … - The Journal of …, 1999 -
Elsevier
A detrusor contraction was initiated at short latency by scratching the skin
or by percutaneous
electrical stimulation in the L7 dermatome. Maximal bladder pressures during
this stimulation
were similar to those activated by bladder distension in control animals. ...
Cited by 57 - Related articles - BL Direct - All 4 versions
An artificial somatic-central nervous system-autonomic reflex pathway for
controllable micturition after spinal cord injury: preliminary results in 15
patients
CG Xiao, MX Du, C Dai, B Li, VW Nitti, WC de … - The Journal of …, 2003 -
Elsevier
... Fig. 1. Skin-CNS-bladder reflex pathway. View Within Article. ... Test
of skin-CNS-bladder reflex
by scratching L5 dermatome caused immediate response of detrusor and
external urethral
sphincter but voiding was not yet synergic and bladder emptying was
incomplete. ...
Cited by 48 - Related articles - BL Direct - All 5 versions
Reinnervation for neurogenic bladder: historic review and introduction of a
somatic-autonomic reflex pathway procedure for patients with spinal cord
injury or spina …
CG Xiao - European urology, 2006 - Elsevier
... related skin. A new concept may be derived from the skin-CNS-bladder
reflex pathway:
the impulses delivered from the efferent neurons of a somatic reflex arc can
be
transferred to initiate responses of an autonomic effector [22]. ...
Cited by 20 - Related articles - All 7 versions
An artificial somatic-autonomic reflex pathway procedure for bladder control
in children with spina bifida
CG Xiao, MX Du, B Li, Z Liu, M Chen, ZH Chen, P … - The Journal of …, 2005
- Elsevier
... through the S2, S3 or S4 VR. The efferent impulses of the skin-CNS-
bladder reflex
pass through the pudendal nerve and should activate the external sphincter
before
the bladder. Therefore, activation of bladder muscle will be ...
Cited by 23 - Related articles - All 3 versions
[PDF] 体神经 2 内脏神经吻合后神经纤维再生过程的光镜电镜观察
zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2002 - 88889595.
zhengdasifuyuan.com
基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出
青年人才基金资助项目(39925033) 作者单位:430022 武汉,华中科技大学同济医学院附
属协和医院泌
尿外科 ... Light microscope and electron microscope study of nerve
regenerated ...
Cited by 17 - Related articles - View as HTML - All 8 versions
[PDF] 人工体神经 2 内脏神经反射弧传出通路神经追踪研究
zhengdasifuyuan.com [PDF]肖传国, 李兵 - 中华实验外科杂志, 2003 - 88889595.
zhengdasifuyuan.com
基金项目:国家自然科学基金重点资助项目(39830370) ;国家杰出 青年人才基金项目(
39925033)
作者单位:430022 武汉,华中科技大学同济医学院附属协和医院泌 尿外科 ... Neural
tracing study
of efferent pathway of the artificial somatic2autonomic reflex arc XIAO
Chuan2guo ,LI ...
Cited by 16 - Related articles - View as HTML - All 6 versions
SKIN-CNS-BLADDER REFLEX ARC FOR MICTURITION AFTER SCI
Chuan-guo Xiao
New York University School Of Medicine New York, Ny 10016
Grant 5R01DK053063-05 from National Institute Of Diabetes And Digestive And
Kidney Diseases IRG: ZRG1
Abstract: The neurological bladder caused by spinal cord injury (SCI)
presents a significant medical and social problem. There is no satisfactory
treatment yet. Supported by the Paralyzed Veterans of America and NIH, a new
reflex pathway, \\\\\\\"Skin-CNS-Bladder\\\\\\\" for controlled micturition
after SCI has been successfully established in rat, cat and canine models.
Preliminary clinical application of 14 SCI patients also provided very
promising results. The study proposed here is to transfer the Skin-CNS-
Bladder reflex functions. The ventral root (VR) of a lumbar nerve (L5) below
the spinal cord lesion will be anastomosed to the sacral VR (S2 and/or S3)
which innervate the bladder, while leaving the intact L5 dorsal root (DR) as
a started of micturition. After the axonal regeneration, controllable
voiding would be initiated by scratching the L4 dermatome. Effect of the new
reflex pathway on bladder function will be evaluated by means of
electrophysiology and urodynamics. Its effect on bowel and sexual functions
will also be studied. The procedure may revolutionize the treatment of
neurogenic bladder after SCI, It requires relatively minor surgery on 2
paralyzed nerves. It does not involve implantation of electrodes or other
devices but provides unique voluntary control of bladder emptying.
Scientifically, the study will further prove the new concept derived from
the unique somatic-autonomic reflex that the impulses delivered from the
efferent neurons of a somatic reflex arc may be transferred to initiate
response of an autonomic effector. This new concept may be widely useful,
not only for neurogenic bladder, but also for other problems caused by the
spinal cord injury or diseases.
Keywords: electrophysiology, human therapy evaluation, neurogenic urinary
bladder disorder, neuroregulation, neurosurgery, somatic reflex, spinal cord
injury, urination, central nervous system, clinical trial, functional
ability, outcomes research, quality of life, skin, urinary electronic
stimulator, clinical research, human subject
Project start date: 1999-09-30
Project end date: 2007-12-31
5R01DK053063-05 (2004): $642796
附录2:中枢神经外周神经的定义和神经再生的理论
The peripheral nervous system, or PNS, consists of the nerves and ganglia
outside of the brain and the spinal cord.[1] The main function of the PNS is
to connect the central nervous system (CNS) to the limbs and organs. Unlike
the CNS, the PNS is not protected by the bone of spine and skull, or by the
blood-brain barrier, leaving it exposed to toxins and mechanical injuries.
The peripheral nervous system is divided into the somatic nervous system and
the autonomic nervous system; some textbooks also include sensory systems.[
2]
Neuroregeneration in the PNS occurs to a significant degree.[5] Axonal
sprouts form at the proximal stump and grow until they enter the distal
stump. The growth of the sprouts are governed by chemotactic factors
secreted from Schwann cells.
Injury to the peripheral nervous system immediately elicits the migration of
phagocytic cells, Schwann cells, and macrophages to the lesion site in
order to clear away debris such as damaged tissue. When a nerve axon is
severed, the end still attached to the cell body is labeled the proximal
segment, while the other end is called the distal segment. After injury, the
proximal end swells and experiences some retrograde degeneration, but once
the debris is cleared, it begins to sprout axons and the presence of growth
cones can be detected. The proximal axons are able to regrow as long as the
cell body is intact, and they have made contact with the neurolemmocytes in
the endoneurial channel. Human axon growth rates can reach 2 mm/day in small
nerves and 5 mm/day in large nerves.[4] The distal segment, however,
experiences Wallerian degeneration within hours of the injury; the axons and
myelin degenerate, but the endoneurium remains. In the later stages of
regeneration the remaining endoneurial tube directs axon growth back to the
correct targets. During Wallerian degeneration, Schwann cells grow in
ordered columns along the endoneurial tube, creating a band of Bungner (boB)
that protects and preserves the endoneurial channel. Also, macrophages and
Schwann cells release neurotrophic factors that enhance re-growth.
Unlike peripheral nervous system injury, injury to the central nervous
system is not followed by extensive regeneration.
附录3:美国William Beaumont医院泌尿外科主任Kenneth M. Peters对肖传国发现的反
射弧手术方法予以综述
Bladder Reinnervation: Is it Becoming a Reality?
Don Bui, Kevin Feber and Kenneth M. Peters
Abstract
Management of neurogenic voiding dysfunction presents a clinical challenge.
Traditional therapies such as clean intermittent catheterization and
antimuscarinics have saved countless lives. However, a desire remains to
normalize the voiding in patients suffering from spinal cord injuries.
Bladder reinnervation is a novel surgical technique that shows promise in
helping those with spinal cord-related neurogenic voiding dysfunction. Dr. C
. G. Xiao from China was the first to popularize bladder reinnervation
through an intradural nerve anastomosis of a lumbar-to-sacral nerve. This
concept has gained international attention, and attempts to create other
somatic-to-autonomic reflex arcs to assist with voluntary voiding have been
studied. In this review, we discuss the current state of the literature in
this new field.
Keywords Neurogenic bladder - Nerve transfer - Incontinence - Spina bifida -
Spinal cord injury
Current Bladder Dysfunction Reports Volume 5, Number 2, 59-62,
附录4:Kenneth M. Peters在美国泌尿学杂志发表论文。报告9名患者的反射弧手术结
果:
THE JOURNAL OF UROLOGY, Vol. 184, 702-708, August 2010
Outcomes of Lumbar to Sacral Nerve Rerouting for Spina Bifida
Kenneth M. Petersa, Benjamin Girdlera, Cindy Turzewskia, Gary Trockc, Kevin
Febera, William Nantaub, Brian Bushb, Jose Gonzaleza, Evan Kassa, Juan de
Benitoa, Ananias Dioknoa
Received 25 November 2009 published online 21 June 2010.
Purpose
Restoring bladder and bowel function in spina bifida by creation of a skin-
central nervous system-bladder reflex arc via lumbar to sacral nerve
rerouting has a reported success rate of 87% in China. We report 1-year
results of the first North American trial on nerve rerouting.
Materials and Methods
Nine subjects were enrolled in the study. Intradural lumbar to sacral nerve
rerouting was performed. Subjects underwent urodynamic testing with
stimulation of the cutaneous dermatome and careful neurological followup.
Adverse events were closely monitored along with changes in bowel and
bladder function.
Results
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle groups at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
Conclusions
At 1 year a novel reflex arc with stimulation of the appropriate dermatome
was seen in the majority of subjects. Improvements in voiding and bowel
function were noted. Lower extremity weakness was mostly self-limited,
except in 1 subject with a persistent foot drop. More patients and longer
followup are needed to assess the risk/benefit ratio of this novel procedure.
Key Words: nerve transfer, spina bifida cystica, spina bifida occulta,
urinary bladder, neurogenic
Abbreviations and Acronyms: DR, dorsal root, EMG, electromyography, VR,
ventral root
http://www.jurology.com/article/S0022-5347(10)03053-3/abstract
附录5:对Kenneth M. Peters论文杂志编辑的评论和论文作者Peter等的回应
EDITORIAL COMMENTS
The Beaumont Hospital in Michigan is one of the first American institutes
that took up clinical trials of the controversial Xiao Procedure. We have
previously questioned their clinical outcomes and their misleading
propaganda in our Open Letter of Complaint against the Xiao Procedure.
More recently, the hospital has also become the first institute to publish
clinical results of Xiao Procedure in an established scientific journal. Dr.
Kenneth Peters and his coauthors wrote in the Journal of Urology of their
results:
At 1 year 7 patients (78%) had a reproducible increase in bladder pressure
with stimulation of the dermatome. Two patients were able to stop
catheterization and all safely stopped antimuscarinics. No patient achieved
complete urinary continence. The majority of subjects reported improved
bowel function. One patient was continent of stool at baseline and 4 were
continent at 1 year. Of the patients 89% had variable weakness of lower
extremity muscle group at 1 month. One child had persistent foot drop and
the remainder returned to baseline by 12 months.
The authors present the first North American experience with lumbar to
sacral nerve rerouting for patients with spina bifida. The results from this
study and previous animal and clinical studies by Xiao clearly demonstrate
that nerve rerouting produces a somatic-autonomic or cutaneous/bladder
reflex with stimulation of the lower extremity dermatome. What is also clear
is that the clinical benefit of the procedure is not at all similar to
previous reports.
Although the authors did an excellent job of following the patients and
characterizing their changes, the results are hard to validate without a
control population going through the same rigorous surveillance regimen. In
particular the improved bowel continence and minimal changes in bladder
compliance may not be statistically significant. The fact that most patients
were still on clean intermittent catheterization and none achieved complete
urinary continence is troubling in light of the report of 87% success with
110 children with spina bifida presented by Xiao. One has to wonder if most
of these children are not voiding volitionally or using the newly developed
cutaneous reflex, and how much reinnervation has a role in this surgery. Is
it possible that unilateral denervation of the S3 ventral motor nerve
produced improved compliance and continence, as previously reported in
numerous clinical series?
I congratulate the authors for taking on this challenge. I hope this study
leads to a rebirth or refocus regarding neurosurgical treatments of
neuropathic bowel and bladder. I strongly agree with the authors that this
procedure should remain on a research protocol only.
Eric A. Kurzrock
Pediatric Urology
U. C. Davis Children’s Hospital
Sacramento, California
One of the most curious findings is the discrepancy between urodynamic data
and subjective voiding. One patient exhibited a decrease in capacity and an
absence of reflex arc, and yet he subjectively reported improved bladder and
bowel function! I could not help but speculate that his voiding after the
procedure could simply be the bladder emptying via intra-abdominal pressure
generation against an open bladder neck, given his preoperative stress
incontinence. Xiao reported that more than 87% of 110 patients gained
sensation and continence within 1 year (reference 7 in article). In
comparison, the current patients undergoing the identical procedure with the
help of Xiao himself only showed a modest improvement in objective
urodynamic studies and subjective reporting. Unless the innovators provide a
sound argument and data for the validity of the procedure, there is a great
danger of its improper and rapid adaptation by patients and the medical
community at large.
John M. Park
Department of Urology
University of Michigan Medical School
Ann Arbor, Michigan
REPLY BY AUTHORS
We agree this is a challenging study on many levels. The intent of
publishing these 1-year data was to understand the potential complications
associated with lumbar to sacral nerve rerouting, demonstrate that a
cutaneous to bladder reflex is achievable and, given the nationwide interest
in this procedure, reinforce the need to continue this rigorous research
protocol until more is known about the risk-benefit profile. Hopefully our
36-month data will shed more light on the clinical usefulness of this
innovative procedure.
附录6:William Beaumont医院泌尿外科2009年底得到美国卫生研究所NIH 230万美元研
究基金
http://projectreporter.nih.gov/project_info_description.cfm?aid