【作者】 常会民；

【导师】 漆松涛；

【作者基本信息】 南方医科大学 ， 神经外科， 2009， 博士

【摘要】 研究背景及目的立体定向精神外科已有60多年的历史,在控制精神病人某些症状方面取得了优良效果,立体定向手术以其创伤小、准确度高,在功能神经外科领域得到越来越广泛的应用。难治性精神病患者因其经常伴有兴奋、冲动、攻击、自杀等行为,对社会、家庭和个人都造成了严重危害,成为精神外科临床研究的主要对象。但是,精神外科自从它诞生的那天起就引起不同的争议,手术疗效不尽相同,手术后患者出现各种各样的并发症,手术后精神病症状的复发率也较高。近年来,随着科技的发展,高精度立体定向手术计划系统和高磁场MRI逐步应用于临床,射频技术也不断提高,对靶点的定位更加准确,手术疗效明显提高,手术对患者造成的损害越来越小,该手术方法已成为难治性精神病的一种有效治疗手段,但远期疗效仍有待于进一步观察,且近年来各种争议越来越大,值得临床进一步研究。难治性精神病的临床疗效欠佳,其中主要原因之一就是其发病机理还不够明确,虽然有各种环路理论和神经递质异常学说,如:由乳头体、隔区、丘脑前核、扣带回、海马、中脑被盖区、内侧嗅区构成的内侧环路功能异常学说等,但是,到目前为止,尚无任何一种学说能够完全解释精神病的发病机制。病理研究发现海马损害在精神分裂症的发生发展中起重要作用,难治性精神病患者海马的神经元数量减少,体积变小,海马神经元的细胞结构受损;海马又紧靠难治性精神病的主要毁损靶点杏仁核,且两者关系密切,对海马的研究具有重要意义。但是对活体海马的研究尚缺乏有效方法。磁共振质子波谱技术（magnetic resonance spectroscopy,MRS）是一种新的活体无创性、无辐射性、利用磁共振现象和化学移位技术测定人脑某些特定部位的一些代谢化合物的方法,是目前唯一可以在活体进行无创性检测细胞水平代谢的检测方法,它可显示某些异常代谢物的出现及一些正常代谢产物含量的异常改变,从20世纪90年代初开始已被广泛用作研究精神疾病的一种新手段。MRS通常测量3种化合物:氮-已酰天门冬氨酸复合物（N-acetylaspartate,NAA）、胆碱复合物（Cholin,Cho）和肌酸-磷酸肌酸复合物（Creatin,Cr）。目前在大多数1H-MRS的研究中主要检测NAA、Cho和Cr在局部脑组织中的浓度。NAA是公认的反应神经元功能的内标物,其浓度改变反映了不同疾病状态下神经元的变化情况。NAA浓度降低可能是由于神经元的破坏减少或线粒体功能失调所致,还可能由于神经元细胞膜的破坏,NHA被暴露于使之降解的酶,因而水解增加所致。NAA浓度降低与神经元或轴突的缺失有明显的相关性。Cho包括胆碱、磷酸甘油胆碱、磷酸胆碱和磷脂酰胆碱,反映脑内总的胆碱量,其浓度的改变反映细胞膜合成和降解的变化。有研究证实,Cho浓度的增高与细胞膜的降解增加引起可溶性Cho浓度的增高相关。Cr包括肌酸与磷酸肌酸,其作为高能磷酸化的储备以及ATP和ADP的缓冲剂可能对维持脑细胞中的能量依赖系统发挥作用。由于Cr在同一个体脑内不同代谢条件下均保持相对稳定,故Cr常作为波谱研究的内参照。以Cr为参照的NAA/Cr和Cho/Cr比值在一定程度上反映了NAA和Cho浓度的变化。通过对精神分裂症患者双侧海马的MRS的代谢特点进行分析,可以对精神分裂症患者的诊断和治疗提供代谢方面依据,为精神分裂症的病因学和手术及药物治疗提供帮助,为新的治疗药物的开发提供线索。但至今为止有关海马NAA、Cho含量的研究差异较大,还有待于进一步探索和研究。研究目的①探讨立体定向手术治疗难治性精神病的有效性,为难治性精神病患者寻找一种有效治疗方法。②探讨立体定向手术治疗难治性精神病的安全性,努力减少各种并发症。③探讨精神分裂症患者海马磁共振质子波谱（¹H-MRS）的变化特点以期对精神分裂症患者的诊断、治疗提供代谢方面依据,为精神分裂症的病因学和治疗措施提供线索。材料和方法1难治性精神病的手术治疗部分的对象与方法对36例难治性精神病患者,男23例,女13例;年龄20岁-56岁,平均（30.2.6±6.8）岁,病程5年-34年,平均（12.2±4.8）年。按照2000年中华医学会精神病学分会制订的《中国精神障碍分类与诊断标准（第三版）》(简称CCMD-3分类标准进行分类。精神分裂症28例,其中,偏执型精神分裂症14例,青春型精神分裂症6例,紧张型精神分裂症5例,未分化型3例。癫痫导致的症状性精神障碍引起的强迫思维、攻击行为4例,心境型精神障碍4例。在36例患者中,有自杀行为者4例,有明显的暴力和攻击行为者3例。手术前,对患者的主要精神症状有精神科医生进行评分,分别采用简明精神病评定量表（the brief psychiatric rating scale BPRS）、阳性症状量表（Scaleassessment of positive scale SAPS）、阴性症状量表（Scale assessment of negativescale SANS）和简明中华成人智力量表（intelligence scale for Chinese adulte,ISCA）评分,便于和手术后评分进行对照。治疗方法:头架为深圳安科公司生产的DSA-602S型立体定向仪,安装头架时多采用局部麻醉,少数不合作者采用全身麻醉。用GE公司生产的1.5T MRI行2mm无间隔薄层扫描行靶点的定位。在确定各个靶点坐标时,为了提高对靶点定位的准确性,采用MRI片直接定位,同时用AC-PC固定坐标中各靶点的坐标进行检验,在两者相差较小时以MRI片中的直接坐标为准,在两者相差较大时,检查直视坐标中所选择的平面是否是所选靶点的最大平面,同时检查确定AC-PC的平面选择的是否准确,注意矫正误差。定位后送手术室在全麻下行靶点毁损,采用双侧钻孔,钻孔点选在冠状蜂前,中线旁开1.5cm-3.5cm。用ASA-601T温控射频热凝仪对靶点进行射频热凝毁损,毁损温度为75℃-80℃,毁损时间为60秒-100秒。射频电极裸露部分有1.6mm×5mm和1.6mm×3mm两种,对隔区的毁损采用1.6mm×3mm的射频电极,对其它靶点的毁损采用1.6mm×5mm的射频电极。选择的靶点组合为:双侧扣带回+双侧杏仁核+双侧内囊前肢18例,双侧扣带回+双侧杏仁核+双侧内囊前肢+双侧内侧隔区12例,双侧扣带回+双侧杏仁核+双侧尾状核下束6例,对扣带回的毁损每侧采用双点毁损,两点之间间隔10mm。手术后将患者的各项观测指标由精神科医生重新评定,皆以患者6个月时观测指标的评分为标准制作表格。总疗效按照1988年全国精神外科协作组制定的疗效评定标准按5级评定法进行评定,Ⅰ-Ⅴ级分别为:恢复、显著进步、进步、无效和恶化,Ⅰ-Ⅲ级称为有效,Ⅳ级、Ⅴ级为无效。所有来院复查的患者均做头颅MRI检查,观察各靶点的毁损范围和毁损靶点的准确度。统计学处理采用SPSS11.0统计软件进行疗效评定,数据采用x±s表示,分别采用两个均数的t检验、统计结果,以P＜0.05作为差异有显著性。2精神分裂症患者海马磁共振质子波谱成像部分的对象与方法20例精神分裂症患者,均符合国际疾病分类第10版的精神分裂症诊断标准,其中,偏执型精神分裂症10例,青春型精神分裂症4例,紧张型精神分裂症3例,未分化型3例。年龄20-34岁,平均年龄（29.6±4.8）岁,病程5-18年,平均11.6±3.6年。所有患者均接受了非典型精神病治疗（如:利培酮、奥氮平、氯氮平）,折合氯丙嗪剂量为（399+156）mg/d,未使用影响脑内乙酰胆碱神经递质的药物。20例对照组人员,均为自愿参加本实验的20名男性健康人,年龄20-42岁,平均年龄为（29.5±5.0）岁,均为右利手。所有检测患者均无头部外伤史、无器质性疾病引起的精神障碍史、无酒精和药物滥用史。波谱数据的采集和后处理:所有的扫描均采用1.5T超导MRI扫描仪（GEMedical System,Milwaukee,USA）完成,机器在扫描前进行数据稳定性的测试。采用泡沫垫进行头部固定,使用标准头线圈作为发射和接收线圈,常规进行轴位、矢状位和冠状位SE T₁WI（TR/TE=476/15ms）和轴位TSET₂WI（TR/TE=3647/100ms）扫描,矩阵256×256,层厚5mm、间距0mm,¹H-MRS采用T₂WI轴位定位于一侧海马选取正方体感兴趣区（VOI）,体素大小为10mm×10mm×10mm,并在轴位、矢状位和冠状位上观察,使所选择的VOI尽量避开侧脑室及脑沟池内的脑脊液。选择点解析波谱序列（PRESS）采集波谱,TR/TE=2000/136ms,激励200次,采集次数为128次。接收、发射增益调节、体素内匀场、水抑制和无水抑制扫描均由自动扫描程序完成,获得波谱后进行基线校正和相位校正。在T₂WI轴位像上的另一侧海马的对称部位选取同样的VOI,用以上的方法采集波谱。所测定的代谢产物主要包括N-乙酰基天门冬氨酸（NAA）、肌酸复合物（Cr）、含胆碱化合物（Cho）。用GE公司提供的软件测量各峰下面积并分别计算NAA/Cr和Cho/Cr比值,并与对照组海马NAA/Cr和Cho/Cr的比值进行对比分析。统计学方法:对所有测量结果利用SPSS11.0软件包进行计算机统计学处理,数据采用x±s表示,分别采用两个均数的t检验,统计结果,以P＜0.05为差异有统计学意义。结果:1手术治疗部分的结果总疗效评定36例患者中,Ⅰ级4例,Ⅱ级28例,Ⅲ级3例,Ⅳ级1例,Ⅴ级0例,总有效率97%。靶点的确认手术后6个月复查头颅MRI发现各毁损靶点部位准确,毁损范围符合术前设计要求。患者术后精神症状大体疗效评定均有明显好转。患者术后简明精神病量表（BPRS）评分均明显下降（手术前BPRS评分为??52.61±9.40;手术后BPRS评分为26.53±8.55 P＜0.01）。患者术后阳性症状量表评分（SAPS）明显下降（术前SAPS评分为26.50±7.44;术后SAPS评分为11.78±2.57 P＜0.01）。术后阴性症状量表评分（SANS）也明显下降（术前SANS评分为27.61±5.35;术后SANS评分为12.75±2.85 P＜0.01）。简明中华成人智力量表（ISCA）测验结果显示手术前后无明显变化（术前ISCA评分282.28±42.10;术后ISCA评分273.03±39.61 P＞0.05）。术后并发症术后出现高热3例,在2-7天内恢复;大小便失禁2例,在2-10天内恢复;一侧肢体肌力下降3例,在2-30天内恢复。2海马磁共振质子波谱成像部分结果患者组在手术治疗前的NAA/Cr值低于正常对照组,患者组在手术治疗前的CHO/Cr值高于正常对照组,（对照组双侧海马的NAA/Cr比值为:左侧1.45±0.13右侧1.44±0.12,患者组双侧海马的NAA/Cr比值为:左侧1.32±0.11右侧1.29±0.14,差异有统计学意义P均＜0.01;对照组双侧海马的CHO/Cr比值为:左侧1.06±0.11右侧1.08±0.13,患者组双侧海马的CHO/Cr比值为:左侧1.14±0.11右侧1.17±0.14,差异有统计学意义P均＜0.01）。结论1手术治疗部分的结论采用多靶点联合毁损术治疗难治性精神病是一种安全有效的治疗方法,近期疗效好,患者的主要精神症状和伴随症状都得到明显缓解,对患者的智力记忆力等功能无显著影响。无肢体瘫痪、昏迷等严重并发症,但对患者精神症状的远期疗效有待于进一步观察。因该手术对脑内各神经核团是一种毁损性手术,毁损后其功能不可逆转,对患者的神经功能的远期影响也还有待于进一步观察。2海马磁共振质子波谱成像部分结论NAA/Cr比值降低和Cho/Cr比值升高表明精神障碍可能都是脑内多种物质代谢系统相互间发生紊乱失调的结果。NAA/Cr比值降低表明海马区神经元数量减少,或存在神经元树突分支减少。CHO/Cr比值升高表明海马区可能存在膜崩解或翻转增加等损害。精神分裂症患者的海马存在神经元的损害和细胞膜代谢异常,支持精神分裂症患者的膜代谢异常学说。展望:由于精神分裂症患者存在海马神经元损害和膜代谢异常,今后,在开发新的治疗药物方面,可在保护细胞膜、促进神经元代谢、减少细胞凋亡、或在转基因药物治疗方面进行更多探索,逐步减少传统抗精神病药物的应用;在手术治疗方面,应多向脑深部电刺激术方面研发,减少脑毁损术的应用。更多还原

【Abstract】 Background and Purposes of the researchStereotactic Psychosurgery has had a history of more than 60 years,which has achieved great effectiveness in controlling some certain symptoms of Psychopathy. stereotactic surgery is becoming widely-used in the functional neurosurgery for its small trauma and high accuracy.Patients with intractable psychopathy always tend to have such behaviors as excitation,impulsion,offensiveness,suicide and so on,which may cause grievous harm to the society,family and the patient himself/herself.Thus, these patients become the major subject for the clinical studies of the Psychosurgery. However,since the very beginning of its emergence,Psychosurgery has gained a great diversity of dispute.There are different kinds of curative effects,with various complications cropped up post-surgery as well as the relatively high recurrence of symptoms.In recent years,with the development of high technology,the systematical plan of high-precision stereotactic surgery and the highfield MRI(Magnetic Resonance Imaging) have been gradually applied in clinical trial.What’s more,the target localization becomes more precise with the constant development of radio-frequency technique.Therefore,Psychosurgery has become an effective method of treatment for the intractable psychopathy,with an obviously improving curative effect and less harm caused by the surgery to the patients.Nevertheless,as this surgical method is receiving more and more disputes,with its long-term curative effects remain further observation,it still needs ever-larger investigation.One main reason for the weak curative effects of the clinical treatment for the intractable psychopathy is the uncertainty of the pathogenesis.Though there are so many Ring Theory and theories about neurotransmitter disorders,e.g.the inner ring road function abnormal theory composed by corpus mamillar,septum area,thalamic nucleus anteriorus,cingulate gyrus,hippocampus,tegmental region of midbrain and inner olfactory region;the pathological studies have found that the injury of hippocampus plays an important role in the occurrence and development of the schizophrenia.The hippocampus neurons of the intractable psychopathy patients will become fewer with its volume getting smaller.All of these will damage the cellular construction.But the study on the living sufferers still lack of effective methods. Magnetic Resonance Spectroscopy is a new method for examining living sufferers, which has been widely-used in kinds of ailment treatment and research.MRS was a new non-ivesive and non-radiation methods,it utilize the magnetic resonance and chemical shift technical to determine some metabolized compounds in the special position of the brain.Up to now,it is the only one method to determine metabolized compounds on cell level in vivid person.It can show some abnormal metabolized compounds and the change of its content.It was used to be a main method to investigate psychopathy from 90 years 20 century.NAA has recognized to be a symbol of nerve cell function,its change of concentration showed the nerve cell change in different disease.NAA concentration reduced may be the cause of nerve cell breakage or reduced.The concentration of CHO increased may be the nerve cell membrane break down.Cr was used to be a hive for high octane phosphate and alleviant for ATP and ADP.Its function was to maintain energy supply for the brain.The level of Cr was always relatively stabilized, it can be used as inner reference for magnetic resonance spectroscopy research.It can collect various data about metabolized compounds.MRS is expected to measure three compounds:N-acetylaspartate,NAA,Cholin,CHO,and Creatin,Cr. Through the analysis of the metabolizing traits of the schizophrenia patients’ bilateral hippocampus,basis on metabolizing can be provided to the surgical treatment on the schizophrenia patients.Besides,it will offer clues for the development of the etiology and treatment mechanism.However,up till now,there still exist great diversity in the research on the content of NAA and CHO of hippocampus.Thus,it remains further investigation and research.Research object:①probing into the validity of curing intractable psychopathy by stereotactic surgery will figure out an effective remedy for intractable psychopath.②probing into the safety of curing intractable psychopathy will be conducive to reduce a variety of syndromes.③probing into the MRS variational features of the psychopath will be expected to provide not only a foundation for the diagnosis,medication and surgery of psychopath in metabolism aspect,but also a clue for the study of psychopathy etiology and the treatment mechanism.Materials and methodsThe object and methods of the intractable psychopathy surgeryAmong 36 intractable psychopaths,males account for 20 while females 16, whose ages are ranged from 20 to 56,averaging(30.2±6.8) years old.And their course of diseases last for 5 to 34 years,averaging(12.2±4.8) years.They will be classified by the classification offered in the Chinese Classification and Diagnostic Criteria of Mental Disorders-Third Edition(CCMD-3),which is formulated by the Psychiatry Branch of Chinese Medical Association in 2000.Accordingly,28 patients suffer from schizophrenia(among the 28 patients,14 patients suffer from the paranoid schizophrenia,6 patients suffer from the Hebephrenic schizophrenia,5 patients suffer from the catatonic schizophrenia,3 patients suffer from the undifferentiated schizophrenia),4 patients suffer from the compulsive thinking and attack caused by symptomatic mental disorder due to epilepsy,and 4 patients suffer from mood disorders.Among 36 patients,4 patients have had suicidal acts,while 3 patients have apparent violence and aggressive acts.Use ANKE Company’s Dsa-602S type stereotactic instrument as the head rack and GE Company’s 1.5T MRI scanned for 2mm thick as the target orientation.To increased the exact position for determine the target lesion,the points of AC and PC should be shown in same slice.The target lesion can be directly localized or refer to standard reference system.When the two methods were distinctly difference,it should be rectification carefully.Use the ASA-601T type radiofrequency thermocoagulation to have a radiofrequency mutilation on the target,with the mutilating temperature ranged from 75 to 80 centigrade and mutilating time ranged from 60 to 100 seconds.The exposed part of radiofrequency electrode have two specifications:1.6mm×5mm and 1.6mm×3mm.We choose the target combination of bilateral cingulate gyrus+ bilateral amygdale+bilateral anterior limb of internal capsule for 18 patients’ treatment,bilateral cingulate gyrus+bilateral amygdale+bilateral anterior limb of internal capsule+bilateral inboard septal area for 12 patients’ treatment,and bilateral cingulate gyrus+bilateral amygdale+bilateral caudate nucleus lower belt for 6 patients’ treatment.Comparing the assessment results previous to the surgery(as patients’ visiting periods are different from each other,their cases will be judged by those in their sixth month and then processed and listed into a form),the overall curative effect will be assessed in light of the standard five-level assessment of therapeutic evaluation formulated by Chinese psychosurgery association in 1988,which fromⅠlevel toⅤlevel will be covering,apparent progress,progress,invalidation and deterioration respectively.Ⅰ-Ⅲlevel is counted as validation,whileⅣlevel andⅤlevel are counted as invalidation.All the patients returning to hospital for further consultation will be given the coronal MRI check as to observe the accurate position and scope of each target.Statistics processingApply the SPSS10.0 statistical software for the therapeutic evaluation.Make an evaluation and statistical analysis of their psychopathy symptom,concise psychopathy scale,concise Brief Psychiatric Rating Scale(BPRS),as well as the masculine and feminine scale through patients’ further consultations or phone inquiries 3 months,6 months,12 months or 24 months after the survey.The object and method of proton magnetic resonance imaging of hippocampus on schizophrenia patientsThe condition of the 20 patients afflicted with schizophrenia all accord with the schizophrenia diagnostic standstards in the tenth edition of international disease category.Among these 20 patients.there are 10 patients suffered from paranoid schizophrenia,4 suffered from hebephrenic schizophrenia,3 suffered from catatonic schizophrenia and 3 suffered from undifferentiated schizophrenia.Their average ages are(29.6±4.8) years,And their course of diseases last for 5 to 18 years,averaging (11.6±3.6) years.Moreover,all of them are right handednesses.In this research,all the patients have received atypical psychosis treatment(such as risperidone,olanzapine, clozapine,etc) with the dose of chlorpromazine amounting to(399+156) mg/d. Moreover,no medicines that affect the acetylcholine in the brain are applied in this experiment.The 20 healthy male who belong to the control group with the average age (29.5±5.0) years old,all volunteer to attend this experiment.Furthermore,all of them belong to right handednesses.In addition,all the tested patients have never suffered from head trauma,organic mental disorders and abuse of alcohol and medicines.The acquisition and post-processing of the spectrum data:all the scannings are compeleted by the MRI of GE Twinspeed 1.5 Ts scanner(GE Medical System, Milwaukee,USA) which has been tested for its data stability before the scannings begin.By using the foam mats for its head fixation and standard head coils for emission and reception,the scanner begin its routine scannings in the position of the axis,sagittal,coronal SE T1WI(TR/TE=476/15ms) and axis TSE T2WI (TR/TE=3647/100ms).The matrix of the scanner is 256×256,the slick thickness of it 5mm and the spacing of it 0mm.1H-MRS is located on the side of the hippocampus by using the T2WI axis.And the VOI,the voxel of which was 10mm×10mm×10mm,is chosen as the region for observation.Moreover,the observation is processed on the position of the axis,the sagittal and the coronal in order to make the chosen VOI avoid the lateral ventricle and the cerebrospinal fluid in the sulcus cell.The point analysis of the sequence of the spectrum is chosen and stimulated for 200 times to collect the spectrum,TR/TE=2000/136ms.The times of the acquisition amount to 128.The reception and the emission of the gain regulation,voxel internal shimming,water suppression and non-water suppression scanning are compeleted by the automatic scanning.After receiving the spectrum,the baseline and the phase are corrected.Then,on the symmetric part of the other side of the hippocampus which is on the T2WI axis image,the same VOI is chosen and spectrum is collected by using the above method.The measured metabolites mainly include NAA,Cr,Cho.The software provided by the GE company is used to measure the area of every mineshita and calculate the ratio of the NAA/Cr and ChO/Cr respectively.Then,a comparative analysis is made between it and ratio of the control group hippocampus NAA/Cr and ChO/Cr.The patients who have received surgical treatment get spectrum analysis according to the method mentioned above after they have ended their surgery for six months.Statistical method:All the measuring results process is processed by the method of computer statistics.The data is represented in the form of x±s.Besides,the pairing t testing,variance analysis and line analysis are applied to measure the experimental results.It will have statistical significance on the condition that P＜0.05.Result:part of the result of the surgeryAccording to the overall therapeutic evaluation,among the 36 patients,there are 4 patients ofⅠlevel,28 ofⅡlevel,3 ofⅢlevel,1 ofⅣlevel,and none ofⅤlevel, with the overall effectiveness amounts to 97 percentages.The recognition of the target:one month after the surgery,when reexamining the head by MRI,we can find all the destroyed targets in the right position,and the destroyed range is within the requirement before the surgery.After the surgery,the mental condition of the patients has significant improvements according to the overall rating of effectiveness.There is a remarked decline of the scores in all the brief psychiatric rating scale(the BPRS pre-operation was 52.61±9.40;aft-operation 26.53±8.55,P＜0.01). There is a noticeable drop of the scores in the positive and negative symptoms(the SANS pre-operation 26.50±7.44;aft-operation 11.78±2.57 P＜0.01.the SAPS pre-operation 27.61±5.35;aft-operation 12.75±2.85 P＜0.01).The intelligent test result indicates that there is no significant change before and after the surgery(the ISCA pre-operation 282.28±42.10;aft-operation 273.03±39.61 P＞0.05).The complication after the surgery:three patients have high fever,and recover within from 2 to 7days;two have the symptoms of fecal and urine incontinence,and both recover within from 2 to 10 days;and three patients suffer from a decline of unilateral muscle strength and recover within from 2 to 30 days.2 part of the result of proton magnetic resonance spectroscopy imaging in hippocampus(~1H-MRS)The NAA /Cr level of the patient groups is lowered than the normal control groups,while the level of CHO/Cr is higher than the normal control groups.(The proportion of NAA/Cr level of bilateral hippocampus:the control groups are 1.45 plus or minus 0.13 at the left side,1.44 plus or minus 0.12 at the right side;the patient groups are 1.32 plus or minus 0.11 and 1.29 plus or minus 0.14.The significant statistical differences,namely P,are both smaller than 0.01.The proportion of the CHO/Cr level:The control groups are 1.06 plus or minus 0.11 at the left side,1.08 plus or minus 0.13 at the right side;the patient groups are 1.14 plus or minus 0.11 and 1.17 plus or minus 0.14.The significant statistical differences,namely P,are both smaller than 0.01.Conclusion1 Part of the conclusion of the surgeryIt is an effective and safe remedy to adopt combined multiple lesions to combat the intractability psychosis.It has a good short-term effectiveness,which can remarkably relieve patients’ main psychiatric symptoms and concomitant symptoms, and has no significant impact on patients’ intelligence and memory.Serious complications such as palsy and coma,further observation of the long-term effectiveness is required.Due to the fact that the surgery is to destroy the nerve nucleus in brain,whose functions are irreversible after the destruction,it also requires the further observation of the long-term impact on the function of nerves.2 Part of the conclusion of 1H-MRSThere are damages in neuron and metabolism disorders in cell membrane in the Hippocampus of schizophrenist.This gives a support to the theory of Membrane Metabolism Disorders.Stereotactic surgery of 1H-MRS exerts unnoticeable influence on the cell membrane in the Hippocampus.Perspect for treatment of intractable Psychopathy:since there are damages in neuron and metabolism disorders in cell membrane in the Hippocampus of schizophrenist,exploiture new drugers in future should be in such direction,protect cell membrance,promote nerve cell metabolize,reduce use traditional anti-Psychopathy drugs.In the way of operation,should reduce use of damage stereotactic surgery,more and more use of deep brain stimulation.更多还原