阿尔茨海默病脑区葡萄糖代谢研究

目的:探讨阿尔茨海默病(AD)患者部分脑区葡萄糖代谢增强的原因及意义. 方法:符合美国精神障碍诊断和统计手册第4版(DSM-4)诊断标准的AD患者33例(AD组),其中17例伴有痴呆精神行为症状(BPSD),16例不伴有BPSD;以20名健康人作对照(对照组).两组均进行一般资料、简易智能状态(MMSE)、日常生活能力及Hachinski缺血指数量表测定,并进行脑正电子发射断层成像(PET)检查;应用SPM2000软件对两组PET图像进行基于像素的比较. 结果:与对照组相比,AD患者左侧额叶内侧回皮质下白质,左侧枕叶楔回灰质(Brodmann 17区)及皮质下白质,右侧小脑扁桃体等脑区葡萄糖代谢显著增强(P<0.001);与不伴有BPSD的AD患者相比,伴有BPSD的AD患者额叶、顶枕叶及颞叶下部等脑区的葡萄糖代谢显著减低(P<0.001),而枕叶、小脑等脑区的代谢显著增强(P<0.001). 结论:无论是否伴有BPSD的AD患者,其脑葡萄糖代谢均有弥漫性减低,但部分脑区呈代谢增强,增强区域主要位于旧皮质,次级运动及感知觉中枢,局部皮质下白质等.AD患者大脑新皮质代谢及高级功能容易受损,而旧皮质及皮质下结构的代谢及功能出现代偿性增强,与BPSD相一致.     

阿尔茨海默病正电子发射计算机断层扫描和神经心理测定的初步研究

目的 探讨阿尔茨海默病(Alzheimer’s disease,AD)的脑葡萄糖代谢、神经心理学特点及AD的正电子发射计算机断层扫描(positron emission photography,PET)诊断。方法 对13例AD患者和11例年龄、性别和文化程度相匹配的健康对照者(HC)进行PET检查、简易智能状态检查(mini-mental state examination,MMSE)、韦克斯勒记忆量表测定(wechsler memory scale,WMS)和日常生活能力量表(activity of daily living,ADL)测定。结果 ①AD组MMSE、WMS分值明显低于HC组(P<0.01)。②肉眼读片,AD组存在脑萎缩,尤其是颞叶萎缩;大脑皮层放射性分布不均匀;健康老人可出现顶叶局部脑葡萄糖代谢率(regional cerebral metabolism rate of glucose,rCMRglc)的减低,但程度较轻;AD组全脑rGMRglc减低,以顶叶为最明显,其次为颞叶,再次为额叶。③AD组在双侧额叶上、中、下回、眶回、直回、颞叶中下回、顶上小叶、缘上回、前扣带回、尾状核、岛叶、丘脑,左侧角回、左侧杏仁核等脑区rCMRglc半定量指标降低较明显,与健康对照组相比,差异具有显著性或高度显著性((P<0.05-P<0.001);AD组病人额叶上中下回葡萄糖代谢半定量指标降低最为明显,其次为丘脑和尾状核。④相关分析表明,MMSE评分与性别呈负相关(P=0.025);右侧顶上小叶和右侧丘脑的rCMRg     

阿尔茨海默病脑白质葡萄糖代谢异常分析

目的探讨阿尔茨海默病(AD)脑白质葡萄糖代谢异常的意义。方法纳入33例符合美国精神障碍诊断与统计手册-第四版(DSM-IV)AD诊断标准的患者和健康对照20名,进行脑正电子发射断层成像(PET)检查。应用SPM软件对PET图像进行分析。结果①与健康对照相比,AD患者有广泛的白质葡萄糖代谢减低,减低较为明显的区域有右侧额叶皮质下白质、左侧额叶上中回皮质下白质(P<0.001);另外,AD患者左侧额叶内侧回皮质下白质、左侧枕叶楔回皮质下白质葡萄糖代谢增强(P<0.001);②与不伴有精神行为症状(BPS)的AD患者(16例)相比,伴有BPS的AD患者(17例)在左右枕叶中回、右侧枕叶楔回、右侧顶下小叶、左侧颞叶梭形回、左侧额叶内侧回等脑区的皮质下白质葡萄糖代谢增强(P<0.001);而左右额叶中央旁回、右侧额叶上回和中回、左侧颞叶上回等脑区的皮质下白质葡萄糖代谢减低(P<0.001)。结论AD有广泛的白质脑葡萄糖代谢异常,有无BPS的AD白质代谢异常不同。     

轻度认知障碍及阿尔茨海默病脑葡萄糖代谢改变的统计参数图的PET研究

目的应用氟脱氧葡萄糖正电子发射计算机断层扫描(18F-FDG PET)探讨阿尔茨海默病(AD)、遗忘型轻度认知障碍(aMCI)患者脑部葡萄糖代谢改变的特点。方法对27例轻度AD患者(AD组)、10例aMCI患者(aMCI组)和21例年龄匹配正常老年志愿者(对照组)行18F-FDG PET成像,对扫描获得的18F-FDG PET图像进行预处理后应用统计参数图(SPM8)对脑葡萄糖代谢进行基于体素水平的组间t检验的统计学分析。结果①与对照组比较,AD组脑葡萄糖代谢减低的脑区包括后扣带回(BA23、31)及楔前叶(BA19)、双侧顶叶(BA40)、双侧颞叶(BA20、21、22、37)、双侧额叶(BA6、9、10)等(P<0.001,未校正,K≥50像素);②AD组与aMCI组比较,脑葡萄糖代谢相对减低的脑区包括后扣带回(BA23、31)及楔前叶(BA19)、颞顶叶(BA40、20、21、22、39)及额叶(BA6、8、9)等(P<0.001,未校正,K≥50体素);③AD组和aMCI组葡萄糖减低的体素数目(12 413个)要少于AD组和对照组的体素数目(17 592个);④aMCI组葡萄糖代谢与对照组比较,仅右侧枕叶的舌回(BA17)减低(P<0.05,未校正)。结论 SPM8可用于诊断和区分AD患者的脑葡萄糖代谢模式。     

脑网络模块化分析用于阿尔茨海默病、路易体痴呆和帕金森病性痴呆脑葡萄糖代谢特点研究

目的本研究探究脑功能成像的脑网络模块化分析在阿尔茨海默病(AD),路易体痴呆(DLB),帕金森病性痴呆(PDD)脑网络模块参数特点和异同点,寻找疾病相关特异性脑葡萄糖代谢网络模块参数。方法回顾性分析复旦大学附属华山医院AD、DLB、PDD组和正常对照组的静息状态18F-FDG PET显像,采用网络模块化分析分别获得4组受试者的脑葡萄糖代谢网络模块化参数,并应用种子点相关分析得到葡萄糖代谢网络连接改变的脑区,比较4组受试者脑代谢网络连接的异同点。结果在稀疏阈值15%时,正常对照组和AD组的网络由4个模块组成,PDD组由6个模块组成,DLB组由10个模块组成。以右侧丘脑为种子点,AD组的颞叶和皮质下脑区连接增强,枕叶和左侧额叶连接减弱。PDD组的额叶、皮质下脑区连接增强,枕叶、颞叶、左侧顶叶的连接减弱。DLB组的左侧额叶和皮质下脑区连接增强,右侧枕叶和顶叶连接减弱。结论 3种不同类型痴呆患者的脑葡萄糖代谢网络具有不同的模块化特性,提示发病机制的差异,为进一步探究其神经机制提供新思路。     

行为变异型额颞叶痴呆患者脑葡萄糖代谢特征研究

目的利用~(18)F-FDG正电子发射断层扫描(PET)成像分析行为变异型额颞叶痴呆(bvFTD)患者脑葡萄糖代谢特征以及在阿尔茨海默病(AD)鉴别诊断中的应用价值。方法纳入临床确诊的bvFTD患者(bvFTD组,14例)、健康对照者(对照组,14例)和AD患者(AD组,14例),先将bvFTD和对照组的PET图像分别进行统计参数图(SPM)及尺度子轮廓模型/主要成分分析(SSM/PCA)分析,获得bvFTD患者脑部葡萄糖代谢图谱并建立bvFTD相关脑代谢网络模式(bvFTDRP);计算bvFTD组、对照组和AD组的bvFTDRP个体表达值,并进行ROC分析。结果 SPM和SSM/PCA分析均显示bvFTD组表现出双侧前额叶和基底节区葡萄糖代谢显著减低。bvFTDRP表达值在3组间差异均有显著统计学意义(ANOVA:F[2,39]=86.663, P0.001),且可有效鉴别bvFTD和AD患者。结论 bvFTD存在与疾病特异相关的脑葡萄糖代谢特征,为~(18)F-FDG PET应用于痴呆诊断提供了客观依据。     

静息状态功能磁共振成像观察轻度阿尔茨海默病后扣带回功能连通性的变化

目的 利用静息状态功能磁共振成像(fMRI)研究阿尔茨海默病(AD)早期后扣带回相关的静息脑网络连通性是如何变化的.方法 运用fMRI研究了16例轻度AD患者和16名健康对照者在静息状态后扣带回的功能连通性.与后扣带回有功能连通性的脑区是通过检测低频波动信号的时程相关性获得的.应用通用的SPM2图像统计软件计算组间和组内连通性差异,激活区阈值设置:P<0.01(校正),像素范围>5.利用SPM2软件随机效应分析t检验(经校正P<0.01,t=2.47,像素范围>5),比较患者组和对照组连通性激活的脑区.结果 与后扣带回有功能连通性减弱的脑区包括前额叶中线区、楔前叶、双侧视皮质、双侧颞下回、左侧海马、右侧丘脑、右侧额叶背外侧区;偏左侧化的连通性增高的脑区包括前额叶中线区、左侧颞下回、左侧基底节区、双侧额叶背外侧区及左侧中央前区.结论 与后扣带回相关的静息状态脑网络连通性减低与AD早期情节记忆损害和高级视觉功能损害有关系,轻度AD保留着功能连接的重塑性以便维持脑功能.静息fMRI是一种探索AD脑功能机制的适宜方法.     

阿尔茨海默病18F-FDG PET显像诊断的研究☆

目的探讨阿尔茨海默病(AD)脑葡萄糖代谢及其18F-脱氧葡萄糖正电子发射计算机断层扫描(18F-FDGPET)显像的影像学特征和PET诊断标准.方法静脉注射18F-FDG后行脑断层显像,检查13例AD、13例非AD痴呆及13例正常人.获得纹状体、丘脑、黑质、顶叶、颞叶、额叶、枕叶、海马单位面积放射性计数与小脑计数的比值(Rcl/cb),进行半定量分析,并与MR进行对照.结果AD患者PET异常率为100%,MR异常者占10/13.PET显像特征①对称性双侧颞顶叶及海马伴额叶或枕叶代谢减低占9例(9/13);②双侧颞叶对称性代谢减低伴海马或额叶代谢下降占3例(3/13);③双顶叶对称性代谢降低1例(1/13).12例(12/13)非AD痴呆表现为不对称、多发性代谢降低,降低区位于黑质、纹状体、丘脑及脑皮质区,MR异常率为11/13.结论在除外脑内结构特异性损害基础上,PET发现对称性双颞顶叶、海马或颞叶、顶叶,伴或不伴枕叶、额叶代谢下降,可诊断AD.PET对AD早期诊断及鉴别诊断具有临床意义.     

AD患者18F-FDG PET/CT脑显像糖代谢改变模式亚型研究

目的 分析阿尔茨海默病(Alzheimer disease, AD)患者¹⁸F-脱氧葡萄糖(fluorodeoxy glucose, FDG)正电子发射断层显像/计算机体层成像(positron emission tomography/computed tomography, PET/CT)脑显像的代谢改变亚型特点,并比较各亚型间临床表现的差异。方法 收集于北京协和医院神经科诊断为很可能AD且β淀粉样蛋白显像为阳性的患者51例(AD组),10名健康体检者作为对照,收集两组受试者¹⁸F-FDG PET/CT脑显像资料,结合视觉分析对AD组与健康对照组¹⁸F-FDG PET/CT图像进行基于体素的定量分析,按主要¹⁸F-FDG代谢减低脑区分布对AD组进行分型,分析各亚型间临床表现的差异。结果 根据代谢减低最明显的部位,将AD组分为边缘系受累为主(A型)、顶颞叶外侧皮层及额叶皮层为主(B型)、后皮质为主(C型)及不对称单侧颞叶受累为主(D型)4种亚型。本组患者以A型组为多见[共31例(61.0%)],均存...     

老年抑郁症患者的脑正电子发射体层摄影术显像分析

目的 探讨老年抑郁症患者脑^18氟-脱氧葡萄糖（18^F-FDG）正电子发射体层摄影术（PET）显像的特点。方法 分别对6例老年抑郁症患者（GD组）及10名健康体检者（对照组）进行脑^18 F-FDGPET显像，按年龄、简易智力状态检查量表总分和性别构成配对，用统计参数图第2版软件比较两组间脑局部葡萄糖代谢的差别。结果 GD组较对照组在双侧尾状核、额下回、颞上回、额中回，右侧核外、额上回、舌回和左侧扣带回、中央前回等脑区局部葡萄糖代谢减低（均P〈0．005）。GD组无局部脑葡萄糖代谢增加的脑区。结论 老年抑郁症患者存在基底节区、前额叶、颞叶和边缘系统的局部葡萄糖代谢下降。     

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.