滋肾调肝法治疗儿童抽动秽语综合征的疗效评价及TS的相关因素分析
|
摘要
研究背景
抽动秽语综合征即Gilles de la Tourette Syndrome(简称TS),又名多发性抽动症(Multiple Tics,MT),是一种慢性神经精神障碍,以不自主肌肉抽动及发声抽动为临床特征。TS确切病因尚未明了,因其临床症状的复杂性、反复性,西药治疗疗效欠佳。文献报道中医治疗本病取得了较好的临床疗效,但因研究未使用RCT(Randomized Clinical Trial)的方法进行系统评价,致使疗效及预后尚未得到严格而令人信服的结果。故以循证医学的方法对本病进行科学、系统的评价是提高疗效的关键。
目的
本课题采用流行病学的研究方法,调查TS发病的高危因素,以指导疾病的防治。分析TS的临床症状,对本病的中医症候、病因病机进行理论探讨。采用随机对照研究,在中医药治疗TS的研究中使用国内外通用的疗效评定量表,并结合自拟中医症候量表,客观评价滋肾调肝法治疗TS的疗效、复发率及安全性,寻找治疗TS安全有效的方法。
方法
本文从基础、理论、临床等多方面评价中医药治疗TS的疗效,并依据流行病学的研究方法,分析本病的相关危险因素。全文分为两个部分。
1.病因病机研究:通过流行病学的方法,以问卷形式,采用病例对照研究,调查160例TS患儿及100例非TS患儿的生活习惯、相关疾病、个人史、家族病史、生活环境等,采用LOGISTIC回归进行病因分析。对相关文献进行系统评价及理论探讨,提出滋肾调肝法为本病的主要治法,并确定课题主要的研究思路及方法。同时分析TS的临床症状,观察运动及发声抽动的临床特点及流行病学特征,临床症状之间的相互关系,调查TS加重因素及伴随的行为障碍、相关疾病等。
2.临床研究:课题设立两个观察中心。根据随机数字表,将160例抽动秽语综合征(TS)门诊患儿随机分为滋肾调肝试验组(80例)、泰必利对照组(80例),引用YGTSS(耶鲁综合抽动严重程度量表)、自拟中医症候量表进行临床观察,记录不良事件表。观察烦躁、精神疲倦、面色萎黄、五心烦热、食欲不振、健忘、出汗异常、大便不调、睡眠障碍、舌脉象等中医症候。耶鲁综合抽动严重程度量表记录运动抽动、发声抽动、综合损害、总体抽动的评分。观察治疗4、8、12周,中医症候的改善情况及耶鲁综合抽动严重程度量表的减分情况,并进行12周疗效评价。半年后随访并记录中医症候表及耶鲁综合抽动严重程度量表,进行疗效评价。
结果
1.病因分析及相关症状的调查
(1)TS发病男性明显高于女性,比例约5.4:1。6～8岁为发病高峰。57.5%的TS患儿出现发声抽动,其中以单音发声及多个单音混合发声为主,分别占总数的25%及30%。头面部眼睛、鼻子、颈、嘴的抽动最为常见,其次为上肢、肩、腹肌、下肢、舌头及眉毛、耳朵。TS最常见的并发症为情绪障碍,占研究总例数的83.1%,其后依次为睡眠障碍、学习障碍。研究同时调查了TS共患ADHD发病率,约占总数的33.8%。反复呼吸道感染及过敏性鼻炎与本病关系密切,外感、情绪刺激及学习紧张可诱发本病加剧。研究未发现TS病情与TS病程及发病年龄的相关性。
(2)病例对照研究发现,围产期损伤及孕母先兆流产、偏食、嗜好游戏及电视、管教严厉、厌食、个性急躁为TS的危险因素。未发现本病同脑外伤、家族精神病遗传、父母多动抽动障碍、单亲家庭等有密切的关系。
(3)TS中医文献系统评价显示:72%的医家同意抽动-秽语综合征的病位在肝。35.3%的学者认为与脾有关,20%认为与肾关系密切。13.3%及7.3%的医家分别认为TS与心、肺相关。少数医家提出本病与胃、胆有关,均占0.7%。内风即肝风在TS的发病中占有主导地位,约72.7%的医家认为内风为TS的主要致病因素,41.8%的文献强调痰在TS发病中的重要作用,其它如火邪、瘀血、食积等因素分别占6.4%、4.5%、2.7%。
(4)病因病机分析:TS病因与先天禀赋不足、情志损害、劳倦过度、饮食失宜、外伤因素有关。基本病机是脏腑功能不足,水不涵木,脾虚肝亢,风动痰扰,病位涉及五脏,但核心当责之于“肝”,与脾、肾密切相关,同心、肺也有一定的关联。标在风痰,本在肝脾肾三脏,虚实并见,风痰并存。
2.疗效评价
(1)滋肾调肝方,滋肾调肝法能有效的改善儿童抽动秽语综合征的烦躁、精神疲倦、面色萎黄、五心烦热、食欲不振、健忘、出汗异常、睡眠障碍、脉象等中医症候。除大便不调、舌象恢复两组症状外,其他各项改善情况均明显优于泰必利组。
(2)滋肾调肝方能明显改善患儿运动抽动、发声抽动,减少患儿的抽动综合损害、耶鲁综合抽动严重程度总分,疗效优于对照组。疗效评定方面,试验组总体抽动痊愈率为12.5%,痊愈显效率为50%,有效率为97.5%;对照组痊愈率为5%,痊愈显效率为18.75%,有效率为65%,两组比较差异有显著的统计学意义(p＜0.01)。试验组在改善运动抽动、发声抽动、综合损害、耶鲁综合抽动严重程度总分等方面均明显优于对照组(p＜0.01)。
(3)半年后随访,滋肾调肝方在改善中医症状及患儿抽动症状方面仍明显优于泰必利组。
(4)未观察到试验药物对心、肝、肾功能及血液系统有异常影响及不良反应,显示了滋肾调肝方良好的安全性。
Background
Tourette's syndrome,I.e Gilles de la Tourette Syndrome(TS),also known as multiple Tic Disorder(Multiple Tics,MT),is a chronic nerve disorder,characterized by involuntary muscle and vocal tic.Etiology of TS is not clear yet,and because of the complexity and recurrent of the clinical symptoms,clinical efficacy is poor.Reports showed good therapeutic effect of Chinese medicine,but the study did not use the method of RCT (Randomized Clinical Trial)to evaluating,then resulting in the effect and prognosis are not been convincde strongly.Therefore,using evidence-based medicine approach,and making a scientific evaluation of the effect,are the key points to raising the clinical effect.
Objective
The obsject of this study including three aspects.First is using epidemiological methods to investigate the risk factors of TS,and help prevention.The second is to analyze the clinical symptoms of TS,and research the theory of TCM Syndrome,and pathogenesis.The third is using randomized single-blind controlled study,combined with domestic and foreign generic rating scale of TS,and self-made Chinese medicine syndrome scale,to make a objective evaluation of the thrapy of nourishing kidney and smothing liver, analyze the relapse rate and security,look for safe and effective treatment methods of TS.
Methods
In this paper,according to basic,theoretical and clinical evidence,we evaluated effect of Chinese medicine to treating TS,and based on epidemiological research methods, analyzed the risk factors of disease.The full text is divided into two parts.
1.Pathogenesis research:According to the approach of epidemiology,using questionnaire forms,case-control method,investigated 160 cases of TS and 100 cases of children without TS.The survey included living habits,related diseases,personal history,family history,living conditions,and then used LOGISTIC regression analysis to making statistics.Made a systematic evaluation of relevant reprots,discussed TCM theories,and then made a propose that the thrapy of nourishing kidney and smothing liver is kidney are closely related with onset of tics.13.3%and 7.3%respectively,physician agreed the heart,the lung related with TS.Liver wind is dominant in pathogenesis of TS,and about 72.7 percent of the physician agreed it is the main risk factors of TS.41.8 percent of the records emphasize sputum.Other such as fire-evil,stagnated blood,stagnation of food occupied the plot ratio of 6.4%,4.5%,2.7%.
(4)Pathogenesis analyses:Innate deficiency,emotional damage,overstrain,improper diet,external injury are concerned with the etiology of TS.The basic pathogenesis of TS is deficiency of viscera,spleen deficiency and liver excessive,water not nurishing wood, wind and sputum stiring up.Disease involving five internal organs,but the liver rulls core responsibilities.The spleen,the kidney closely related to disease,and the heart and the lung have some relevance too.The foundation of TS are the spleen,the kidney and the liver,wind and sputum are outside manifest of TS.The excess and the deficiency,the wind and the sputum are coexisted.
2.Evaluation of curative effect
(1)The soup of Zishen Tiaogan,method of nourishing kidney and smothing liver relieved following symptome in TS,including irritability,mental fatigue,etiolate complexion,feverish sensation of five centres,loss of appetite,forgetfulness,sweating abnormalities,sleep disorders,pulse in Chinese medicine.In addition to the abnormal stool and tongue,all improved better than tiapride group.
(2)The soup of Zishen Tiaogan relieved movement tic,vocal tic,reduce comprehensive damage,the overall score using the scale of YGTSS,the effect is better than the control group.Clinical assessment showed the test group recovery rate was 12.5 percent, recovered and obvious efficiency rate was 50%,and effective power was 97.5%.For the control group the recovery rate was 5 percent,recovered and obvious efficiency rate was 18.75%,the effective power was 65 percent.There is a high degree of statistical significance between two gruops(p＜0.01).The test group was obviously better than the control group(p＜0.01).
(3)The soup of Zishen Tiaogan was obviously better than the control group(p＜0.01)in improving the TCM symptoms and relieving tics,after Six months later follow-up.
(4)we did not find adverse impact and abnormal reaction on the heart,the liver,the kidney and blood system,The soup of Zishen Tiaogan.showed high security in clinical test.
抽动秽语综合征即Gilles de la Tourette Syndrome(简称TS),又名多发性抽动症(Multiple Tics,MT),是一种慢性神经精神障碍,以不自主肌肉抽动及发声抽动为临床特征。TS确切病因尚未明了,因其临床症状的复杂性、反复性,西药治疗疗效欠佳。文献报道中医治疗本病取得了较好的临床疗效,但因研究未使用RCT(Randomized Clinical Trial)的方法进行系统评价,致使疗效及预后尚未得到严格而令人信服的结果。故以循证医学的方法对本病进行科学、系统的评价是提高疗效的关键。
目的
本课题采用流行病学的研究方法,调查TS发病的高危因素,以指导疾病的防治。分析TS的临床症状,对本病的中医症候、病因病机进行理论探讨。采用随机对照研究,在中医药治疗TS的研究中使用国内外通用的疗效评定量表,并结合自拟中医症候量表,客观评价滋肾调肝法治疗TS的疗效、复发率及安全性,寻找治疗TS安全有效的方法。
方法
本文从基础、理论、临床等多方面评价中医药治疗TS的疗效,并依据流行病学的研究方法,分析本病的相关危险因素。全文分为两个部分。
1.病因病机研究:通过流行病学的方法,以问卷形式,采用病例对照研究,调查160例TS患儿及100例非TS患儿的生活习惯、相关疾病、个人史、家族病史、生活环境等,采用LOGISTIC回归进行病因分析。对相关文献进行系统评价及理论探讨,提出滋肾调肝法为本病的主要治法,并确定课题主要的研究思路及方法。同时分析TS的临床症状,观察运动及发声抽动的临床特点及流行病学特征,临床症状之间的相互关系,调查TS加重因素及伴随的行为障碍、相关疾病等。
2.临床研究:课题设立两个观察中心。根据随机数字表,将160例抽动秽语综合征(TS)门诊患儿随机分为滋肾调肝试验组(80例)、泰必利对照组(80例),引用YGTSS(耶鲁综合抽动严重程度量表)、自拟中医症候量表进行临床观察,记录不良事件表。观察烦躁、精神疲倦、面色萎黄、五心烦热、食欲不振、健忘、出汗异常、大便不调、睡眠障碍、舌脉象等中医症候。耶鲁综合抽动严重程度量表记录运动抽动、发声抽动、综合损害、总体抽动的评分。观察治疗4、8、12周,中医症候的改善情况及耶鲁综合抽动严重程度量表的减分情况,并进行12周疗效评价。半年后随访并记录中医症候表及耶鲁综合抽动严重程度量表,进行疗效评价。
结果
1.病因分析及相关症状的调查
(1)TS发病男性明显高于女性,比例约5.4:1。6～8岁为发病高峰。57.5%的TS患儿出现发声抽动,其中以单音发声及多个单音混合发声为主,分别占总数的25%及30%。头面部眼睛、鼻子、颈、嘴的抽动最为常见,其次为上肢、肩、腹肌、下肢、舌头及眉毛、耳朵。TS最常见的并发症为情绪障碍,占研究总例数的83.1%,其后依次为睡眠障碍、学习障碍。研究同时调查了TS共患ADHD发病率,约占总数的33.8%。反复呼吸道感染及过敏性鼻炎与本病关系密切,外感、情绪刺激及学习紧张可诱发本病加剧。研究未发现TS病情与TS病程及发病年龄的相关性。
(2)病例对照研究发现,围产期损伤及孕母先兆流产、偏食、嗜好游戏及电视、管教严厉、厌食、个性急躁为TS的危险因素。未发现本病同脑外伤、家族精神病遗传、父母多动抽动障碍、单亲家庭等有密切的关系。
(3)TS中医文献系统评价显示:72%的医家同意抽动-秽语综合征的病位在肝。35.3%的学者认为与脾有关,20%认为与肾关系密切。13.3%及7.3%的医家分别认为TS与心、肺相关。少数医家提出本病与胃、胆有关,均占0.7%。内风即肝风在TS的发病中占有主导地位,约72.7%的医家认为内风为TS的主要致病因素,41.8%的文献强调痰在TS发病中的重要作用,其它如火邪、瘀血、食积等因素分别占6.4%、4.5%、2.7%。
(4)病因病机分析:TS病因与先天禀赋不足、情志损害、劳倦过度、饮食失宜、外伤因素有关。基本病机是脏腑功能不足,水不涵木,脾虚肝亢,风动痰扰,病位涉及五脏,但核心当责之于“肝”,与脾、肾密切相关,同心、肺也有一定的关联。标在风痰,本在肝脾肾三脏,虚实并见,风痰并存。
2.疗效评价
(1)滋肾调肝方,滋肾调肝法能有效的改善儿童抽动秽语综合征的烦躁、精神疲倦、面色萎黄、五心烦热、食欲不振、健忘、出汗异常、睡眠障碍、脉象等中医症候。除大便不调、舌象恢复两组症状外,其他各项改善情况均明显优于泰必利组。
(2)滋肾调肝方能明显改善患儿运动抽动、发声抽动,减少患儿的抽动综合损害、耶鲁综合抽动严重程度总分,疗效优于对照组。疗效评定方面,试验组总体抽动痊愈率为12.5%,痊愈显效率为50%,有效率为97.5%;对照组痊愈率为5%,痊愈显效率为18.75%,有效率为65%,两组比较差异有显著的统计学意义(p＜0.01)。试验组在改善运动抽动、发声抽动、综合损害、耶鲁综合抽动严重程度总分等方面均明显优于对照组(p＜0.01)。
(3)半年后随访,滋肾调肝方在改善中医症状及患儿抽动症状方面仍明显优于泰必利组。
(4)未观察到试验药物对心、肝、肾功能及血液系统有异常影响及不良反应,显示了滋肾调肝方良好的安全性。
Background
Tourette's syndrome,I.e Gilles de la Tourette Syndrome(TS),also known as multiple Tic Disorder(Multiple Tics,MT),is a chronic nerve disorder,characterized by involuntary muscle and vocal tic.Etiology of TS is not clear yet,and because of the complexity and recurrent of the clinical symptoms,clinical efficacy is poor.Reports showed good therapeutic effect of Chinese medicine,but the study did not use the method of RCT (Randomized Clinical Trial)to evaluating,then resulting in the effect and prognosis are not been convincde strongly.Therefore,using evidence-based medicine approach,and making a scientific evaluation of the effect,are the key points to raising the clinical effect.
Objective
The obsject of this study including three aspects.First is using epidemiological methods to investigate the risk factors of TS,and help prevention.The second is to analyze the clinical symptoms of TS,and research the theory of TCM Syndrome,and pathogenesis.The third is using randomized single-blind controlled study,combined with domestic and foreign generic rating scale of TS,and self-made Chinese medicine syndrome scale,to make a objective evaluation of the thrapy of nourishing kidney and smothing liver, analyze the relapse rate and security,look for safe and effective treatment methods of TS.
Methods
In this paper,according to basic,theoretical and clinical evidence,we evaluated effect of Chinese medicine to treating TS,and based on epidemiological research methods, analyzed the risk factors of disease.The full text is divided into two parts.
1.Pathogenesis research:According to the approach of epidemiology,using questionnaire forms,case-control method,investigated 160 cases of TS and 100 cases of children without TS.The survey included living habits,related diseases,personal history,family history,living conditions,and then used LOGISTIC regression analysis to making statistics.Made a systematic evaluation of relevant reprots,discussed TCM theories,and then made a propose that the thrapy of nourishing kidney and smothing liver is kidney are closely related with onset of tics.13.3%and 7.3%respectively,physician agreed the heart,the lung related with TS.Liver wind is dominant in pathogenesis of TS,and about 72.7 percent of the physician agreed it is the main risk factors of TS.41.8 percent of the records emphasize sputum.Other such as fire-evil,stagnated blood,stagnation of food occupied the plot ratio of 6.4%,4.5%,2.7%.
(4)Pathogenesis analyses:Innate deficiency,emotional damage,overstrain,improper diet,external injury are concerned with the etiology of TS.The basic pathogenesis of TS is deficiency of viscera,spleen deficiency and liver excessive,water not nurishing wood, wind and sputum stiring up.Disease involving five internal organs,but the liver rulls core responsibilities.The spleen,the kidney closely related to disease,and the heart and the lung have some relevance too.The foundation of TS are the spleen,the kidney and the liver,wind and sputum are outside manifest of TS.The excess and the deficiency,the wind and the sputum are coexisted.
2.Evaluation of curative effect
(1)The soup of Zishen Tiaogan,method of nourishing kidney and smothing liver relieved following symptome in TS,including irritability,mental fatigue,etiolate complexion,feverish sensation of five centres,loss of appetite,forgetfulness,sweating abnormalities,sleep disorders,pulse in Chinese medicine.In addition to the abnormal stool and tongue,all improved better than tiapride group.
(2)The soup of Zishen Tiaogan relieved movement tic,vocal tic,reduce comprehensive damage,the overall score using the scale of YGTSS,the effect is better than the control group.Clinical assessment showed the test group recovery rate was 12.5 percent, recovered and obvious efficiency rate was 50%,and effective power was 97.5%.For the control group the recovery rate was 5 percent,recovered and obvious efficiency rate was 18.75%,the effective power was 65 percent.There is a high degree of statistical significance between two gruops(p＜0.01).The test group was obviously better than the control group(p＜0.01).
(3)The soup of Zishen Tiaogan was obviously better than the control group(p＜0.01)in improving the TCM symptoms and relieving tics,after Six months later follow-up.
(4)we did not find adverse impact and abnormal reaction on the heart,the liver,the kidney and blood system,The soup of Zishen Tiaogan.showed high security in clinical test.
引文
[1]刘智胜,林庆.抽动秽语综合征的神经心理研究进展.国外医学儿科分册,1994:21(3):116.
[2]赖世隆,杨小波,温泽淮,等.症候宏观诊断标准基本框架的探讨.中国中西医结合杂志,2005;25(6):556.
[3]ShapiroE,Shapiro.Semiology.nosology,and criteria for ticdisorders.Rev Neurol,1986;14(2):824.
[4]Kadesjo B,Gillberg C.Tourette's isorder:epidemiology and comorbidity in primary school children.J Am Acad Child Adolesc Psychiatry,2000:39:548.
[5]Shapiro AK,ShapirQ ES,Young JG,Feinberg TE.Gills de la Tourette Syndrome,York:Raven Press,1988:23.
[6]张骠.小儿多发性抽动症中医证治特点及其研究述略[J].江苏中医药,2004;(25)9:1.
[7]王文革,孟宪军.汪受传治疗小儿多发性抽动症的经验.辽宁中医杂志,2004;31(3):181.
[8]刘瑞芹.毕可恩治疗小儿病验案[J].山东中医杂,2001:20(2):1172.
[9]孙孝登,邱文菁.中医辨证分型治疗抽动—秽语综合征[J].中国中西医结合杂志,2001;21(5):3781.
[10]陆磊.大风珠加味治疗抽动秽语综合征12例[J].湖北中医杂志,2001;23(7):281.
[11]刘唐义.中医治疗阴虚风动性抽动秽语综合征的研究与应用.中国临床康复,2005;(20):168.
[12]苗晋,苗琦.抽动-秽语综合征的中医治疗.陕西中医函授,2002;(2):1.
[13]赖东兰,李宜瑞.李宜瑞教授治疗儿童抽动-秽语综合征经验述要.中医药学刊,2002;(7):1176.
[14]龚人爱.老中医经验宣桂琪治疗抽动-秽语综合征经验撷萃.江苏中医药,2004;25(5):8.
[15]于忠翠,林海霞.育肝息风汤治疗小儿抽动秽语综合征.中国中医急症,2005;14(4):305.
[16]张春玲,刘志杰.刘弼臣治疗抽动-秽语综合征经验.山东中医杂志,2005:24(1):52.
[17]李润荣.温胆汤加减治疗儿童抽动症[J].上海中医药杂志,1996;30(1):131.
[18]谢昌仁.平肝清胃法治疗小儿抽动秽语综合征[J].时珍国医国药,2000:11(1):51.
[19]Parks,et al.The early course of the Tourette syndrome clinical speltum.Neurology,1993;48:1712.
[20]Holzer JC.et al.Sleep disorder in Tourette syndrome:A primary or unrelated problem? AnnNeurol,1990;28:424.
[21]Singer Hs,et al.Obsessive Compulsive disorder with and without a disorders comparison in 70 Patients.Br J chronic tic Psychiatry,1994:164:469.
[22]艾小文,马传红,王立华.抽动—秽语综合征病理生理学研究进展.山东医药,1998:38(11):43.
[23]BohlhalterS,GoldfineA,MattesonS,GarrauxG,HanakawaT,KansakuK,Wurzman R,Hallett M.Neural correlates of tic generation in Tourette syndrome:an event-related functionalMRI study.Brain,2006;V129NPt8:2029.
[24]PlessenKJ,LundervoldA,GrunerR,HammarA,LundervoldA,PetersonBS,Hugdahl K.Functional brain asymmetry,attentional modulation,and interhemispheric transfer in boys with Tourette syndrome.Neuropsychologia,2007;V45N4:767.
[25]Garraux G,Goldfine A,Bohlhalter S,Lerner A,Hanakawa T,Hallett M.Increased midbrain gray matter inTourette's syndrome..AnnNeurol,2006;V59N2;381.
[26]YoonDY,Gause CD,LeckmanJF,SingerHS.Frontaldopaminergicabnormality in Tourette syndrome:a postmortem analysis.JNeurolSci,2007;V255N1-2:50.
[27]Amat JA,Bronen RA,Saluja S,Sato N,Zhu H,Gorman DA,Royal J,Peterson BS.Increased number of subcortical hyper intensities on MRI in children and adolescents with Tourette's syndrome,obsessive-compulsive disorder,and attention deficit hyperactivity disorder.Am J Psychiatry,2006;V163N6:1106.
[28]Swain JE,Scahill L,Lombroso PJ,King RA,Leckman JF.Tourette syndrome and tic disorders:a decade of progress.J Am Acad Child Adolesc Psychiatry,2007;V46N8-:947.
[29]Chen CK,Chen SL,Mill J.The dopamine transporter gene is associated with attention deflect hyperactivity disorder in a Taiwanese sample[J].Mol sychiatry,2003;8(4):393.
[30]Mihara K,Kondo T,Yasui Furukori N,et al.Dopamine D2 receptor gene polymorphisms and clinical response to selective dopamine receptor antagonists[C].InternationalCongress Series,2002;1244(1):77.
[31]ComingsDE,ComingsBG,Muhlen.D,etal.TheDopamineD2receptor locus A modifying in neuropsychiatric disorders JAMA,1991;266:1793.
[32]程宇航,郑毅,王力芳,等.多巴胺D4受体基因多态性与抽动秽语综合症的关联性分析.中国药理学会通讯,2002:19(1):25.
[33]Yoon DY,Rippel CA,Kobets AJ,Morris CM,Lee JE,Williams PN,Bridges DD,Vandenbergh DJ,Shugart YY,Singer HS.Dopaminergic polymorphisms in Tourette syndrome:association with the DAT gene(SLC6A3).Am J Med Genet B Neuropsychiatr Genet,2007;V144N5:605.
[34]文霞.Torrette综合征神经递质研究进展.国外医学精神病学神经外科学分册,1997;24(3):142.
[35]孙道开.抽动和抽动—秽语综合征.国外医学儿科分册,1985:2:81.
[36]GoidenGs.Tics,Twitches and habit spasms.Curr problpediatr,1978;8:29.
[37]Wassman ER,et al:Gilles de la tourette syndrome clinical and genetic studies in a midwestern city.Neurology,1978;28;304.
[38]ShapiroAK,et al.A pediatricion's guide,Bay Side New York,1980;1.
[39]刘智胜.第三届国际多发性抽动症研讨会侧记[J].实用儿科临床杂志,2000;15(6):355.
[40]Pringsheim T,DavenportWJ,Lang A.Tics with Group A streptococcal infections. Neurology,2003;16(4):523.
[41]Church AJ,Dale RC,Lees AJ,et al.Tourette's syndrome:a cross sectional study to examine the PANDAS hypothesis.J NeurolNeurosurg Psychiatry,2003;74(5):602.
[42]Swedo SE,Leonard HL,Kiessling LS.Speculations on anti2—neuronal antibody mediatedneurop sychiatric disorders ofchildhood.J Pediatrics,1994;93(2):323.
[43]Gardona F,Orefici G.Group A streptococcal infections and tic disorders in an Italian pediatricpopulation.JPediatr,2001;138(1):71.
[44]KawikovaI,LeckmanJF,KronigH,KatsovichL,Bessen DE,Ghebremiehael M,Bothwell AL.Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome:a preliminary study.Biol Psychiatry,2007;V61N3:273.
[45]文红.抽动-秽语综合征危险因素的LOGISTIC回归分析.四川精神卫生,1997;10(1):31-32.
[46]尹公礼,白雪光,臧德馨.巨细胞病毒感染与Tourette综合征.临床精神医学杂志,1999:(3):139.
[47]GormanDA,ZhuH,AndersonGM,DaviesM,PetersonBS.Ferritinlevels and their association with regional brain volumes in Tourette's syndrome.Am J Psychiatry,2006;V163N7:1264.
[48]Rindner EC.Living with Tourette's syndrome.J Psychosoc Nurs Ment Health Serv,2007;V45NS:19.
[49]Rizzo R,Curatolo P,Gulisano M,Virzi M,Arpino C,Robertson MM.Disentangling the effects of Tourette syndrome and attention deficit hyperactivity disorder on cognitive and behavioral phenotypes.BrainDev,2007;V29N7:413.
[50]王文革,孟宪军.汪受传治疗小儿多发性抽动症的经验.辽宁中医杂志,2004;31(3):181.
[51]黄宇虹,马融.辨证分型治疗抽动障碍的临床观察.天津中医药,2003;20(2):76.
[52]赵明德,董春桂.中西医结合治疗小儿抽动秽语综合征43例疗效观察.新中医,2002:34(5):36.
[53]尹传清,刘守兰.中西医结合治疗抽动—秽语综合征65例.辽宁中医杂志,2000;27(7):313.
[54]肖旭腾,刘洪校.定风定神汤治疗儿童抽动症46例疗效观察.新中医,2001;33(10):20.
[55]杨丽新.培土抑木法治疗小儿抽动秽语综合征36例.浙江中西医结合杂志,2001:11(9):575.
[56]李利斌.益脑胶囊与补肾益脑片联用治疗小儿抽动秽语综合征37例.中国中医药信息杂志,2003:10(12):61.
[57]徐荣谦.小儿抽动—秽语语综合征从肺论治52例分析.中医杂志,1993:34(11):678.
[58]封玉琳.平肝化痰健脾活血治疗小儿抽动秽语综合征89例.上海中医药杂志,2002;36(12):16.
[59]郭乃琴,聂鸿丹.针刺加耳穴贴压治抽动秽语综合征39例[J].上海针灸杂志,2002:(21):31.
[60]王有鹏,姜桂云,田双蓉.针药结合治疗小儿抽动—秽语综合征23例.针灸临床杂志,1998:14(1):17.
[61]杜连澎.穴位注射治愈—例多动性抽动综合征.四川中医,1995;10:54.
[62]陈德林.针刺加制动散贴脐治疗抽动秽语综合征5例.新中医,1994;26(7):38.
[63]梁玉辉,徐杰,刘军.针刺拔罐加耳穴贴压治疗儿童抽动秽语综合征52例.中国针灸,1998;5:276.
[64]刘智胜,林庆.Tourette综合征.国外医学精神病分册,1994:21(2):99.
[65]Muller Vahl KR.The benzamides tiapride,sulpiride,and amisulpride in treatment for Tourette's syndrome.Nervenarzt,2007:V78N3:264.
[66]SalleeFR,RockCM.ActaPsychiatric Scand,1994:90(1):4.
[67]Chappell PB,Scahill LD.Leckman JF.Neurol Clin,1997:15(2):429.
[68]Gerlach J,PeacockL.IntClin Psychopharmacology,1995:10(Supp13):39.
[69]熊光润,陈静,冯玲.泰必利联合西比灵治疗抽动障碍临床分析.中国临床医学杂志,2004:(5):64.
[70]郑亚兵,宋雄.泰必利和氟哌啶醇治疗多发性抽动症依从性比较.广西中医院学报,2002:5(2):22.
[71]谢小玲,伍大华,彭旭.胃复安控制抽动秽语综合征及改善认知功能的研究.中国神经精神疾病杂志,2002:28(4):256.
[72]谭庆荣,李彦华,吴保仁,等.利培酮治疗抽动秽语综合征25例.第四军医大学学报,2002:23(7):662.
[73]李万田,陈淑平.转移因子等综合治疗儿童抽动秽语综合征.中华神经精神科杂志,1994;(2):18.
[74]朱梅芳.德巴金控释片治疗30例抽动秽语综合征疗效观察.福建医药杂志,1997;19(6):64.
[75]黄明镜,关国清.卡马西平,硝基安定治疗抽动秽语综合征20例报告[J].脑与神经疾病杂志,1999;7(5):267.
[76]Gilbert DL,Zhang J;Lipps TD,Natarajan N,Brandyberry J,Wang Z,Sallee FR,Wassermann EM.Atomoxetine treatment of ADHD in Tourette syndrome:reduction in motor cortex inhibition correlates with clinical improvement.Clin Neurophysiol,2007:V118NS:1835.
[77]吕永良,钱连华.Tourette综合征的外科治疗.国外医学精神病学分册,1996;23(2):99.
[78]袁树斌,雷进,唐秩,庞晓霞,周家全,廖述才.旋转式伽马刀治疗抽动秽语综合征1例报告.立体定向和功能性神经外科杂志,2000;13(3):143.
[79]王秀伟,张剑宁,章翔.抽动秽语综合征立体定向治疗1例报告.立体定向和功能性神经外科杂志,1999;12(4):64.
[80]张晓化,李勇杰.立体定向手术治疗难治性抽动秽语综合征[J].立体定向和功能性神经外科杂志,2004;17(2):88.
[81]SingerHS.Currentissues in Tourette syndrome.Mov Disorder 2000,15(6):1051.
[82]Bloch MH,Peterson BS,Scahill L,Otka J,Katsovich L,Zhang H,Leckman JF.Adulthood outcome of tic and obsessive-compulsive symptom severity in children withTourette syndrome.Arch PediatrAdolesc Med,2006;V160N1:65.
[83]王健,谭钊安,林节.Tourette综合征患者6～12年的随访研究.中华精神科杂志,1999:32(1):62.
[84]钱连华,华于静.Tourette综合征患者9～12年随访研究.中国神经精神疾病杂志,1996;22(6):357.
[85]Leckman,Riddle,Hardin.The Yale Global Tic Severity Scale.J Am Acad Child AdolescPsychiatry,1989;28:566.
[86]Harcherlk D,Ltckman J F,Detlor J,etal.A New Instrument for Clincal Studies of Tourette Syndrome.J Am Acak Child Psychiatry,1984;23:15.
[87]Singer HS,Giuliano JD,Zimmerman AM,et al.lnfection:A stimulus for tic disorders.Pediatr Neurol,2000;22:380.
[88]KurlanR.Tourette'ssyndrome:currentconcepts.Neurology,1989;39:1625.
[89]胡平.电视所致抽动障碍18例资料分析.临床精神医学杂志,2005;15(4):208.
[90]李树华,庞保东,徐应军.抽动—秽语综合征危险因素的病例对照研究.中国儿童保健杂志,2004:(12)5:412.
[91]魏宝玉,金正勇,李今子.抽动障碍儿童家庭环境.中国妇幼保健,2007;22:4848.
[92]刘智胜.小儿多发性抽动症,北京:人民卫生出版社,2002:73.
[93]孙正伟.振腹疗法治疗儿童多动症、抽动症.吉林中医药,2005:25(5):47.
[2]赖世隆,杨小波,温泽淮,等.症候宏观诊断标准基本框架的探讨.中国中西医结合杂志,2005;25(6):556.
[3]ShapiroE,Shapiro.Semiology.nosology,and criteria for ticdisorders.Rev Neurol,1986;14(2):824.
[4]Kadesjo B,Gillberg C.Tourette's isorder:epidemiology and comorbidity in primary school children.J Am Acad Child Adolesc Psychiatry,2000:39:548.
[5]Shapiro AK,ShapirQ ES,Young JG,Feinberg TE.Gills de la Tourette Syndrome,York:Raven Press,1988:23.
[6]张骠.小儿多发性抽动症中医证治特点及其研究述略[J].江苏中医药,2004;(25)9:1.
[7]王文革,孟宪军.汪受传治疗小儿多发性抽动症的经验.辽宁中医杂志,2004;31(3):181.
[8]刘瑞芹.毕可恩治疗小儿病验案[J].山东中医杂,2001:20(2):1172.
[9]孙孝登,邱文菁.中医辨证分型治疗抽动—秽语综合征[J].中国中西医结合杂志,2001;21(5):3781.
[10]陆磊.大风珠加味治疗抽动秽语综合征12例[J].湖北中医杂志,2001;23(7):281.
[11]刘唐义.中医治疗阴虚风动性抽动秽语综合征的研究与应用.中国临床康复,2005;(20):168.
[12]苗晋,苗琦.抽动-秽语综合征的中医治疗.陕西中医函授,2002;(2):1.
[13]赖东兰,李宜瑞.李宜瑞教授治疗儿童抽动-秽语综合征经验述要.中医药学刊,2002;(7):1176.
[14]龚人爱.老中医经验宣桂琪治疗抽动-秽语综合征经验撷萃.江苏中医药,2004;25(5):8.
[15]于忠翠,林海霞.育肝息风汤治疗小儿抽动秽语综合征.中国中医急症,2005;14(4):305.
[16]张春玲,刘志杰.刘弼臣治疗抽动-秽语综合征经验.山东中医杂志,2005:24(1):52.
[17]李润荣.温胆汤加减治疗儿童抽动症[J].上海中医药杂志,1996;30(1):131.
[18]谢昌仁.平肝清胃法治疗小儿抽动秽语综合征[J].时珍国医国药,2000:11(1):51.
[19]Parks,et al.The early course of the Tourette syndrome clinical speltum.Neurology,1993;48:1712.
[20]Holzer JC.et al.Sleep disorder in Tourette syndrome:A primary or unrelated problem? AnnNeurol,1990;28:424.
[21]Singer Hs,et al.Obsessive Compulsive disorder with and without a disorders comparison in 70 Patients.Br J chronic tic Psychiatry,1994:164:469.
[22]艾小文,马传红,王立华.抽动—秽语综合征病理生理学研究进展.山东医药,1998:38(11):43.
[23]BohlhalterS,GoldfineA,MattesonS,GarrauxG,HanakawaT,KansakuK,Wurzman R,Hallett M.Neural correlates of tic generation in Tourette syndrome:an event-related functionalMRI study.Brain,2006;V129NPt8:2029.
[24]PlessenKJ,LundervoldA,GrunerR,HammarA,LundervoldA,PetersonBS,Hugdahl K.Functional brain asymmetry,attentional modulation,and interhemispheric transfer in boys with Tourette syndrome.Neuropsychologia,2007;V45N4:767.
[25]Garraux G,Goldfine A,Bohlhalter S,Lerner A,Hanakawa T,Hallett M.Increased midbrain gray matter inTourette's syndrome..AnnNeurol,2006;V59N2;381.
[26]YoonDY,Gause CD,LeckmanJF,SingerHS.Frontaldopaminergicabnormality in Tourette syndrome:a postmortem analysis.JNeurolSci,2007;V255N1-2:50.
[27]Amat JA,Bronen RA,Saluja S,Sato N,Zhu H,Gorman DA,Royal J,Peterson BS.Increased number of subcortical hyper intensities on MRI in children and adolescents with Tourette's syndrome,obsessive-compulsive disorder,and attention deficit hyperactivity disorder.Am J Psychiatry,2006;V163N6:1106.
[28]Swain JE,Scahill L,Lombroso PJ,King RA,Leckman JF.Tourette syndrome and tic disorders:a decade of progress.J Am Acad Child Adolesc Psychiatry,2007;V46N8-:947.
[29]Chen CK,Chen SL,Mill J.The dopamine transporter gene is associated with attention deflect hyperactivity disorder in a Taiwanese sample[J].Mol sychiatry,2003;8(4):393.
[30]Mihara K,Kondo T,Yasui Furukori N,et al.Dopamine D2 receptor gene polymorphisms and clinical response to selective dopamine receptor antagonists[C].InternationalCongress Series,2002;1244(1):77.
[31]ComingsDE,ComingsBG,Muhlen.D,etal.TheDopamineD2receptor locus A modifying in neuropsychiatric disorders JAMA,1991;266:1793.
[32]程宇航,郑毅,王力芳,等.多巴胺D4受体基因多态性与抽动秽语综合症的关联性分析.中国药理学会通讯,2002:19(1):25.
[33]Yoon DY,Rippel CA,Kobets AJ,Morris CM,Lee JE,Williams PN,Bridges DD,Vandenbergh DJ,Shugart YY,Singer HS.Dopaminergic polymorphisms in Tourette syndrome:association with the DAT gene(SLC6A3).Am J Med Genet B Neuropsychiatr Genet,2007;V144N5:605.
[34]文霞.Torrette综合征神经递质研究进展.国外医学精神病学神经外科学分册,1997;24(3):142.
[35]孙道开.抽动和抽动—秽语综合征.国外医学儿科分册,1985:2:81.
[36]GoidenGs.Tics,Twitches and habit spasms.Curr problpediatr,1978;8:29.
[37]Wassman ER,et al:Gilles de la tourette syndrome clinical and genetic studies in a midwestern city.Neurology,1978;28;304.
[38]ShapiroAK,et al.A pediatricion's guide,Bay Side New York,1980;1.
[39]刘智胜.第三届国际多发性抽动症研讨会侧记[J].实用儿科临床杂志,2000;15(6):355.
[40]Pringsheim T,DavenportWJ,Lang A.Tics with Group A streptococcal infections. Neurology,2003;16(4):523.
[41]Church AJ,Dale RC,Lees AJ,et al.Tourette's syndrome:a cross sectional study to examine the PANDAS hypothesis.J NeurolNeurosurg Psychiatry,2003;74(5):602.
[42]Swedo SE,Leonard HL,Kiessling LS.Speculations on anti2—neuronal antibody mediatedneurop sychiatric disorders ofchildhood.J Pediatrics,1994;93(2):323.
[43]Gardona F,Orefici G.Group A streptococcal infections and tic disorders in an Italian pediatricpopulation.JPediatr,2001;138(1):71.
[44]KawikovaI,LeckmanJF,KronigH,KatsovichL,Bessen DE,Ghebremiehael M,Bothwell AL.Decreased numbers of regulatory T cells suggest impaired immune tolerance in children with tourette syndrome:a preliminary study.Biol Psychiatry,2007;V61N3:273.
[45]文红.抽动-秽语综合征危险因素的LOGISTIC回归分析.四川精神卫生,1997;10(1):31-32.
[46]尹公礼,白雪光,臧德馨.巨细胞病毒感染与Tourette综合征.临床精神医学杂志,1999:(3):139.
[47]GormanDA,ZhuH,AndersonGM,DaviesM,PetersonBS.Ferritinlevels and their association with regional brain volumes in Tourette's syndrome.Am J Psychiatry,2006;V163N7:1264.
[48]Rindner EC.Living with Tourette's syndrome.J Psychosoc Nurs Ment Health Serv,2007;V45NS:19.
[49]Rizzo R,Curatolo P,Gulisano M,Virzi M,Arpino C,Robertson MM.Disentangling the effects of Tourette syndrome and attention deficit hyperactivity disorder on cognitive and behavioral phenotypes.BrainDev,2007;V29N7:413.
[50]王文革,孟宪军.汪受传治疗小儿多发性抽动症的经验.辽宁中医杂志,2004;31(3):181.
[51]黄宇虹,马融.辨证分型治疗抽动障碍的临床观察.天津中医药,2003;20(2):76.
[52]赵明德,董春桂.中西医结合治疗小儿抽动秽语综合征43例疗效观察.新中医,2002:34(5):36.
[53]尹传清,刘守兰.中西医结合治疗抽动—秽语综合征65例.辽宁中医杂志,2000;27(7):313.
[54]肖旭腾,刘洪校.定风定神汤治疗儿童抽动症46例疗效观察.新中医,2001;33(10):20.
[55]杨丽新.培土抑木法治疗小儿抽动秽语综合征36例.浙江中西医结合杂志,2001:11(9):575.
[56]李利斌.益脑胶囊与补肾益脑片联用治疗小儿抽动秽语综合征37例.中国中医药信息杂志,2003:10(12):61.
[57]徐荣谦.小儿抽动—秽语语综合征从肺论治52例分析.中医杂志,1993:34(11):678.
[58]封玉琳.平肝化痰健脾活血治疗小儿抽动秽语综合征89例.上海中医药杂志,2002;36(12):16.
[59]郭乃琴,聂鸿丹.针刺加耳穴贴压治抽动秽语综合征39例[J].上海针灸杂志,2002:(21):31.
[60]王有鹏,姜桂云,田双蓉.针药结合治疗小儿抽动—秽语综合征23例.针灸临床杂志,1998:14(1):17.
[61]杜连澎.穴位注射治愈—例多动性抽动综合征.四川中医,1995;10:54.
[62]陈德林.针刺加制动散贴脐治疗抽动秽语综合征5例.新中医,1994;26(7):38.
[63]梁玉辉,徐杰,刘军.针刺拔罐加耳穴贴压治疗儿童抽动秽语综合征52例.中国针灸,1998;5:276.
[64]刘智胜,林庆.Tourette综合征.国外医学精神病分册,1994:21(2):99.
[65]Muller Vahl KR.The benzamides tiapride,sulpiride,and amisulpride in treatment for Tourette's syndrome.Nervenarzt,2007:V78N3:264.
[66]SalleeFR,RockCM.ActaPsychiatric Scand,1994:90(1):4.
[67]Chappell PB,Scahill LD.Leckman JF.Neurol Clin,1997:15(2):429.
[68]Gerlach J,PeacockL.IntClin Psychopharmacology,1995:10(Supp13):39.
[69]熊光润,陈静,冯玲.泰必利联合西比灵治疗抽动障碍临床分析.中国临床医学杂志,2004:(5):64.
[70]郑亚兵,宋雄.泰必利和氟哌啶醇治疗多发性抽动症依从性比较.广西中医院学报,2002:5(2):22.
[71]谢小玲,伍大华,彭旭.胃复安控制抽动秽语综合征及改善认知功能的研究.中国神经精神疾病杂志,2002:28(4):256.
[72]谭庆荣,李彦华,吴保仁,等.利培酮治疗抽动秽语综合征25例.第四军医大学学报,2002:23(7):662.
[73]李万田,陈淑平.转移因子等综合治疗儿童抽动秽语综合征.中华神经精神科杂志,1994;(2):18.
[74]朱梅芳.德巴金控释片治疗30例抽动秽语综合征疗效观察.福建医药杂志,1997;19(6):64.
[75]黄明镜,关国清.卡马西平,硝基安定治疗抽动秽语综合征20例报告[J].脑与神经疾病杂志,1999;7(5):267.
[76]Gilbert DL,Zhang J;Lipps TD,Natarajan N,Brandyberry J,Wang Z,Sallee FR,Wassermann EM.Atomoxetine treatment of ADHD in Tourette syndrome:reduction in motor cortex inhibition correlates with clinical improvement.Clin Neurophysiol,2007:V118NS:1835.
[77]吕永良,钱连华.Tourette综合征的外科治疗.国外医学精神病学分册,1996;23(2):99.
[78]袁树斌,雷进,唐秩,庞晓霞,周家全,廖述才.旋转式伽马刀治疗抽动秽语综合征1例报告.立体定向和功能性神经外科杂志,2000;13(3):143.
[79]王秀伟,张剑宁,章翔.抽动秽语综合征立体定向治疗1例报告.立体定向和功能性神经外科杂志,1999;12(4):64.
[80]张晓化,李勇杰.立体定向手术治疗难治性抽动秽语综合征[J].立体定向和功能性神经外科杂志,2004;17(2):88.
[81]SingerHS.Currentissues in Tourette syndrome.Mov Disorder 2000,15(6):1051.
[82]Bloch MH,Peterson BS,Scahill L,Otka J,Katsovich L,Zhang H,Leckman JF.Adulthood outcome of tic and obsessive-compulsive symptom severity in children withTourette syndrome.Arch PediatrAdolesc Med,2006;V160N1:65.
[83]王健,谭钊安,林节.Tourette综合征患者6～12年的随访研究.中华精神科杂志,1999:32(1):62.
[84]钱连华,华于静.Tourette综合征患者9～12年随访研究.中国神经精神疾病杂志,1996;22(6):357.
[85]Leckman,Riddle,Hardin.The Yale Global Tic Severity Scale.J Am Acad Child AdolescPsychiatry,1989;28:566.
[86]Harcherlk D,Ltckman J F,Detlor J,etal.A New Instrument for Clincal Studies of Tourette Syndrome.J Am Acak Child Psychiatry,1984;23:15.
[87]Singer HS,Giuliano JD,Zimmerman AM,et al.lnfection:A stimulus for tic disorders.Pediatr Neurol,2000;22:380.
[88]KurlanR.Tourette'ssyndrome:currentconcepts.Neurology,1989;39:1625.
[89]胡平.电视所致抽动障碍18例资料分析.临床精神医学杂志,2005;15(4):208.
[90]李树华,庞保东,徐应军.抽动—秽语综合征危险因素的病例对照研究.中国儿童保健杂志,2004:(12)5:412.
[91]魏宝玉,金正勇,李今子.抽动障碍儿童家庭环境.中国妇幼保健,2007;22:4848.
[92]刘智胜.小儿多发性抽动症,北京:人民卫生出版社,2002:73.
[93]孙正伟.振腹疗法治疗儿童多动症、抽动症.吉林中医药,2005:25(5):47.