NGF联合自体骨髓干细胞动员治疗重型颅脑损伤疗效观察

目的探讨神经生长因子(NGF)联合自体骨髓干细胞(BMSCs)动员治疗重型颅脑损伤的临床疗效和安全性。方法选取60例重型颅脑损伤患者按随机数字表分为对照组(30例,给予NGF和综合康复治疗)和观察组(30例,在对照组治疗基础上加用自体BMSCs动员治疗),比较2组患者神经功能缺损评分(NIHSS)、格拉斯哥预后评分(GOS)及不良反应。结果 2组患者治疗28d的NIHSS评分均较治疗前明显降低(P<0.05),且观察组较对照组降低更为显著(P<0.05);观察组伤后6个月GOS评分明显高于对照组(P<0.05),外周血CD34+、CD133+占外周血单核细胞比率治疗3周时明显高于对照组(P<0.05)。2组患者均未出现明显不良反应。结论 NGF联合自体BMSCs动员及综合康复治疗可促进重型颅脑损伤患者神经损伤的修复,显著改善患者神经功能。     

自体骨髓干细胞动员联合醒脑静治疗脑损伤临床研究

目的探讨自体骨髓干细胞(BMSCs)动员联合醒脑静治疗颅脑损伤的临床疗效和安全性。方法选取郑州市第七人民医院神经外科收治的颅脑损伤患者67例,按随机数字表分为对照组34例和观察组33例,治疗组在对照组基础上加用醒脑静联合自体BMSCs动员治疗,治疗前后采用格拉斯哥评分(GCS)和神经功能缺损评分(NIHSS)评价疗效,采用流式细胞术检测外周血CD133+/CD34+比例,观察不良反应。结果治疗后观察组GCS评分明显升高,NIHSS评分明显降低,外周血CD34CD133占外周血单核细胞比率升高显著,与对照组比较差异具有统计学意义(P0.05),治疗及随访期间均未出现明显不良反应。结论自体BMSCs动员联合醒脑静可有效促进颅脑损伤患者神经损伤修复,显著改善患者神经功能。     

5000/自体骨髓干细胞动员移植与手术移植治疗脊髓损伤的实验研究

探讨自体骨髓干细胞( bone marrow stem cells, BMSC)动员移植与手术移植治疗脊髓损伤（spinal cord injury，SCI）的疗效和机制。方法：选用10周龄健康SD大鼠90只，雌雄各半，建模前注射5-溴2-脱氧尿嘧啶核苷 (Bromodeoxyuridine,Brdu) 50mg/kg/d×3天后抽取自体骨髓，体外分离自体BMSC；NYU(New York University，NYU) Impactor制作SCI模型，随机分为对照组、动员移植组、手术移植组各30只。动员移植组应用重组粒细胞刺激因子（granulocyte-colony stimulating factor,G-CSF）皮下注射，20mg/kg/d×7天；手术移植组为损伤局部移植0.3ml（1×107个/ml）BMSC,各组均从术前三天开始，连续10天腹腔注射Brdu 50mg/kg/d。采用Basso-Beattie-Bresnahan（BBB）评分检测大鼠后肢的运动功能；体感诱发电位（somatoseneory evoked potential,SEP）和运动诱发电位（motor evoke potential,MEP）检测脊髓上、下行神经传导通路，判断SCI和恢复程度；病理和免疫组化观察脊髓损伤组织细胞结构变化及Brdu、GFAP和NSE分布表达。结果：BBB评分1周以后动员移植组和手术移植组分别较对照组比较差异有统计学意义（p＜0.05）,SEP、MEP潜伏期和波幅2周后动员移植组和手术移植组较对照组比较差异有统计学意义，组织病理学显示动员移植组和手术移植组较对照组有更少的空洞、坏死及GFAP阳性胶质瘢痕组织，较多的Brdu阳性细胞和NSE阳性细胞。结论：自体BMSCs动员移植和手术移植两种方法均能明显减轻SCI的程度，促进损伤后的脊髓功能的恢复，二者对比，前者更为方便、无创，实用性强，更有可能抓住有限的治疗时机，因而应用前景可能更好。     

鼠神经生长因子治疗视神经挫伤的疗效观察

目的探讨注射用鼠神经生长因子治疗视神经挫伤的临床疗效及对视觉诱发电位(VEP)的影响。方法选取68例(68眼)视神经挫伤患者为研究对象,随机分为观察组和对照组各34例(34眼)。对照组给予糖皮质激素及维生素类药物治疗;观察组在对照组基础治疗上给予注射用鼠神经生长因子30μg+2mL灭菌注射用水肌内注射,1次/d,疗程6周。对比2组患者治疗前后视力、中心视野灰度、VEP潜伏期和波幅、不良反应发生情况。结果治疗后观察组总有效率91.18%明显高于对照组70.59%,差异具有统计学意义(P0.05);2组患者治疗后视力均得到好转、中心视野灰度均下降、VEP潜伏期均缩短和波幅均增加,观察组优于对照组,差异具有统计学意义(P0.05);2组治疗过程中无不良反应(P0.05)。结论注射用鼠神经生长因子对视神经挫伤临床治疗效果显著,有助于患者视力恢复及VEP的改善,安全性高,值得应用。     

实验性内囊出血后脊髓前角缝连接对肌痉挛的影响

目的:观察大鼠脑出血后脊髓运动神经无缝隙连接(gap junction,GJ)对肌痉挛的影响。方法:采用自体血脑内注入法制备大鼠内囊出血致肌痉挛模型,检测皮质运动诱发电位(Motor Evoked Potential,MEP),应用免疫组化方法观察脊髓前角运动神经元连接蛋白C_x32的改变。结果:大鼠内囊出血后病灶侧MEP波幅较对侧显著降低(P<0.01),且出血后1周病灶侧波幅较出血前显著降低(P<0.01);MEP潜伏期显著延长(P<0.01)。脑出血后第1周,左侧脊髓灰质前角GJ蛋白C_x32显著升高,同时动物肌痉挛状态明显加重。结论:内囊定向的脑出血模型引起内囊损伤侧MEP波幅明显降低、潜伏时延长,脊髓前角运动神经元GJ数量增多。     

脑卒中病人磁性刺激运动诱发电位改变的初步探讨(附27例正常对照)

本文应用磁性刺激的新技术对34例脑卒中病人作运动诱发电位(MEP)检查,并与CT 资料及正常人作对照分析。结果发现不同的临床肌力皮层 MEP 表现各有差异。临床肌力4～5°的21例中,CT 无明显异常改变者9例;皮层 MEP 潜伏期延迟,但波幅改变与对照组无差异。肌力0～3°的13例中,CT 无明显异常改变者4例,皮层 MEP 之潜伏期和波幅有明显变化。本文资料说明 MEP 对检测运动传导系统的功能状态更正确而可靠。     

体感诱发电位及运动诱发电位对脊髓型颈椎病患者脊髓功能的诊断价值

目的探讨体感诱发电位(somatosensory evoked potentials,SEP)及经颅电刺激运动诱发电位(motor evoked potentials,MEP)对脊髓型颈椎病患者脊髓功能的诊断价值。方法利用诱发电位仪对31例脊髓型颈椎病患者术前、术后SEP及MEP检测,分别记录SEP、MEP潜伏期及相应的波幅值,并与临床症状改善情况进行比较。结果 31例患者中术前SEP、MEP异常率分别为90.3%(28例)、54.8%(17例),4周检测异常率分别为35.3%(11例)、19.4%(6例)。与正常组比较,患者组潜伏期和波幅差异有统计学意义(P0.05)。与患者术前比较,术后4周的潜伏期和波幅改善差异有统计学意义(P0.05),与临床表现的改善相关(P0.05)。患者中SEP和MEP潜伏期及中枢传导时间(CMCT)均异常时,其临床表现较重。结论 SEP和MEP相结合可以判断脊髓功能受损的严重程度,为脊髓型颈椎病提供客观诊断及预后依据。     

自体骨髓干细胞移植联合神经营养因子治疗帕金森病的疗效

目的：初步探讨自体骨髓干细胞（bone marrow stem cell ,BMSCs）动员移植联合神经营养因子治疗帕金森病的安全性及疗效。方法将106例 PD患者随即分为对照组与观察组,对照组在口服美多巴基础上给予鼠神经生长因子（mNGF）肌内注射,1次/d ,连续4周;观察组在对照组治疗基础上行BMSCs动员移植治疗,6个月后采用 Hoehn-Yahr分期评分、UPDRS评分、改良Webster量表评定2组疗效。结果 BMSCs动员移植联合神经营养因子在改善患者运动症状及平衡障碍、日常活动及行为,精神、情绪等非运动症状方面较单用神经营养因子疗效更佳。结论自体骨髓干细胞动员移植联合神经营养因子治疗帕金森病安全,疗效满意。     

经颅电刺激运动诱发电位监测麻醉方法的建立

目的 对比相同麻醉深度下丙泊酚、七氟醚分别复合瑞芬太尼维持麻醉对经颅电刺激运动诱发电位(TES-MEPs)波幅和潜伏期的影响,以建立术中MEP监测时的适宜麻醉方法.方法 36例脊髓脊柱神经外科手术患者随机分为两组:丙泊酚麻醉组和七氟醚麻醉组,每组18例.对比麻醉诱导后30 min、60 min、90 min和120 min MEP的波幅和潜伏期.结果 两组病例麻醉期间血流动力学均维持稳定,组间脑电双频指数、呼气末二氧化碳分压和体温的差异均无统计学意义.丙泊酚组MEP所需阈刺激强度显著低于七氟醚组[(172±23)V:(217±42)V,P＜0.05].丙泊酚组各时间点上肢MEP波幅显著高于七氟醚组(P＜0.05),潜伏期显著短于七氟醚组(P＜0.05).两组内各时间点上肢MEP波幅和潜伏期差异无统计学意义.结论 在相同麻醉深度下,丙泊酚复合瑞芬太尼全凭静脉麻醉对MEP波幅的抑制作用显著优于七氟醚复合瑞芬太尼静吸复合麻醉方案,是用于脊髓脊柱手术TES-MEPs监测的适宜麻醉方法.     

人尿激肽原酶对急性脑梗死皮层运动诱发电位的影响

目的 本课题采用经颅磁刺激运动诱发电位(motor evoked potential,MEP)的方法,了解人尿激肽原酶对急性脑梗死患者运动功能恢复的影响.方法 64例急性脑梗塞患者,随机分为试验组(34例)及对照组(30例),在起病72 h之内,试验组给予人尿激肽原酶(0.15 PNA单位)静脉滴入,在使用药物治疗(14±3)d前后,进行经颅磁刺激运动诱发电位检查,对比观察两组患者治疗前后患侧中枢传导时间(central motor conduction time, CMCT)及皮层运动诱发电位(motor evoked potential,MEP)波幅变化.结果 治疗前,两组患者皮层MEP引出率、波幅及CMCT均无明显差异(P＞0.05).治疗后,试验组皮层MEP引出率、波幅与对照组比较仍无明显差异(P＞0.05);试验组下肢皮层MEP引出率的增高程度(14.7%)明显高于对照组(6.7%)P＜0.05);试验组上肢CMCT(7.6±2.28)ms较对照组(9.0±2.80)ms明显缩短(P＜0.05);试验组下肢MEP波幅 [2.5(1.3,5.7)]mv较对照组下肢[1.9(0.7,5.3)]mv明显增高(P＜0.05).结论 人尿激肽原酶对急性脑梗死患者中枢运动传导的恢复有一定促进作用.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

Hepatic Considerations in the Use of Antiepileptic Drugs

Summary: Virtually all of the major antiepileptic drugs (AEDs) can cause hepatotoxicity, although fatal hepatic reactions are rare. The mechanisms, incidences, and risk profiles for such reactions differ from drug to drug. With carbamazepine and phenytoin, hepatotoxicity may be due to drug hypersensitivity. Although the profiles of patients at risk have not been well-defined for these two antiepileptic drugs, it would appear from reports in the literature that older adolescents and adults are at higher risk than children of developing serious or fatal hepatotoxicity. Once hepatotoxicity develops, mortality rates are 10–38% with phenytoin and 25% for carbamazepine. The risk profile for valproate fatal hepatotoxicity has been more clearly defined. Those at primary risk of fatal hepatic dysfunction are children under the age of 2 years who are receiving multiple anticonvulsants and also have significant medical problems in addition to severe epilepsy. The risk is considerably lower for patients over the age of 2 years on valproate monotherapy. In contrast to the risk profile with other AEDs, adults receiving valproate as monotherapy have the lowest risk of hepatotoxicity. Fatal hepatic dysfunction coincident with valproate may be the result of aberrant drug metabolism. Concomitant use of AEDs that induce microsomal P450 enzymes (e.g., phenytoin and phenobarbital) may enhance the production of a toxic metabolite, and hence the greater risk of hepatotoxicity with polypharmacy.     

Vascular Malformations and Epilepsy: Clinical Considerations and Basic Mechanisms

Summary: Vascular malformations (VMs) are associated with epilepsy. The natural history of the various VMs, clinical presentation, and tendency to provoke epilepsy determine treatment strategies. Investigations have probed the mechanisms of epileptogenesis associated with these lesions. Electrophysiologic changes are associated with epileptogenic cortex adjacent to VMs. Putative pathophysiologic mechanisms of epileptogenesis include neuronal cell loss, glial proliferation and abnormal glial physiology, altered neurotransmitter levels, free radical formation, and aberrant second messenger physiology.     

Neonatal Seizures: Problems in Diagnosis and Classification

Summary: The clinical identification of neonatal seizures is critical for the recognition of brain dysfunction; however, diagnosis is often difficult because of the poorly organized and varied nature of these behaviors. Current classification systems are limited in their ability to communicate motor, autonomic, and electroencephalo-graphic features of seizures precisely and to provide a basis for uniform effective diagnosis, therapy, and determination of prognosis. Recent investigations of neonates, utilizing bedside electroencephalographic/polygraphic/ video monitoring techniques, have provided the basis for improved diagnosis and classification of seizures in the newborn. These studies have demonstrated that not all clinical phenomena currently considered to be seizures require electrocortical epileptiform activity for their initiation or elaboration. In addition, the specific clinical character of the phenomena considered to be seizures, the clinical state of the infant, and the character of the EEG indicate the probable pathophysiological mechanisms involved and suggest probable etiologies, prognosis, and therapy. Similarities between animal models that demonstrate reflex physiology and neonates with motor automatisms and tonic posturing suggest that these clinical behaviors may not be epileptic in origin but, rather, primitive movements of progression and posture mediated by brainstem mechanisms. Although not all clinical behaviors currently considered to be neonatal seizures may have similar pathophysiological mechanisms, they are clinically significant because they all indicate brain dysfunction.     

Valproate Monotherapy in the Management of Generalized and Partial Seizures

Summary: For decades, therapeutic tradition has promoted the concept of polypharmacy in the management of epilepsy. In recent years, however, studies have shown that, for most patients, monotherapy can provide comparable or better seizure control than administration of multiple anticonvulsants, while diminishing the potential for adverse reactions, drug interactions, and poor compliance. Valproate is an important monotherapeutic agent that is highly effective in the control of idiopathic primary and secondarily generalized epilepsies, and partial seizures that do not generalize. Comparative studies have found that valproate is at least as effective as phenytoin and carbamazepine in the treatment of generalized and partial seizures. Given the similar efficacy, other factors such as pharmacokinetics and side effects may therefore determine anticonvulsant selection for monotherapy.     

Carbamazepine Efficacy and Utilization in Children

Summary: Carbamazepine is effective for preventing partial and generalized tonic-clonic seizures in children. Although absence epilepsies are more common in children than adults, an estimated 80% of children with epilepsy have seizure types or epilepsies that are potentially responsive to carbamazepine. The differential diagnosis of ictal staring is an especially important issue in children because absence and atypical absence seizures are more prevalent in children than adults. Age-related pharmacokinetic differences and drug interactions are major considerations in children. On average, children have higher clearance rates of carbamazepine, shorter half-lives, and higher ratios of carbamazepine-10, 11-epoxide to carbamazepine than adults. In addition, children with severe epilepsy are more likely to require multiple-drug therapy, which can lead to complex drug interactions. When carbamazepine is administered along with valproate, drug protein binding interactions can cause intermittent side effects.     

Un nouveau cadre conceptuel de travail pour la psychiatrie

In an attempt to place psychiatric thinking and the training of future psychiatrists more centrally into the context of modern biology, the author outlines the beginnings of a new intellectual framework for psychiatry that derives from current biological thinking about the relationship of mind to brain. The purpose of this framework is twofold. First, it is designed to emphasize that the professional requirements for future psychiatrists will demand a greater knowledge of the structure and functioning of the brain than is currently available in most training programs. Second, it is designed to illustrate that the unique domain which psychiatry occupies within academic medicine, the analysis of the interaction between social and biological determinants of behavior, can best be studied by also having a full understanding of the biological components of behavior.