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.     

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。     

阿尔茨海默病~(18)F-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-FDG PET）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。     

Diagnostic Difficulties and Treatment Implications

Summary: Differentiation between types of epileptic seizures has been aided in recent years by the introduction of intensive neurodiagnostic techniques and the development of increasingly detailed classification systems. Paradoxically, these developments have not simplified the task of matching the appropriate antiepileptic drug to a particular seizure type. It is reasonable to assume that anticonvulsant drugs will have different effects on different types of seizures, but faulty, circular reasoning can enter the picture if one also assumes that responses of seizures to different drugs signify different seizure types. There are several examples of differential diagnoses that can fall prey to this problem, including the diagnosis between partial seizures with secondary generalization and generalized tonic-clonic seizures, and the diagnosis between complex partial seizures and absence seizures with automatisms, among others. Considerations of etiology in future classification systems can further complicate the problem: should one then choose an anticonvulsant drug on the basis of individual seizure type or on the basis of the type of epilepsy? Ramifications of this issue extend even to the drug approval process. Official sanction is not given for use of a drug for a seizure type not included in the original efficacy studies, even if later scientific evidence shows that seizure type to be related to a type that is included. New trials must be undertaken. These problems arise from how we choose to classify seizures.     

Cognitive Dysfunction Associated with Antiepileptic Drug Therapy

Summary: Epilepsy is frequently associated with cognitive dysfunction. However, the reasons for this correlation are unclear. Possible influential factors include patient age; duration, frequency, etiology, and type of seizures; hereditary factors; psychosocial issues; and antiepileptic drug (AED) therapy. Whereas many of these factors are beyond the physician's control, AED therapy is one element that can be addressed in treatment decisions by recognizing the potential cognitive effects of particular AEDs. For example, phenobarbital impairs memory and concentration; phenytoin affects attention, problem solving ability, and performance of visuomotor tasks. In contrast, carbamazepine may affect concentration, while valproate would appear to have minimal effects on cognition. Moreover, cognitive effects of AEDs are amplified with coadministration of multiple anticonvulsants (polytherapy). A review of studies on the cognitive effects of monotherapy with AEDs, as opposed to those of polytherapy, provides evidence that drug-related cognitive dysfunction can be reversed if patients are switched to a simpler therapeutic regimen. Future research should be directed toward developing reliable measures for assessing and monitoring cognition, and understanding the particular cognitive side effects of each AED. Physicians also need to revise their opinions about which side effects are "tolerable" for epileptic patients.     

Carbamazepine Efficacy in Adults With Partial and Generalized Tonic-Clonic Seizures

Summary: Carbamazepine and phenytoin are drugs of choice in initial monotherapy for adult partial and secondarily generalized tonic-clonic seizures. These designations reflect the results of the Veterans Administration Epilepsy Cooperative Study Group of 1985. An earlier comparative study of carbamazepine and phenytoin by Ramsay and associates found both drugs equally effective in controlling new-onset seizures. Among the advantages of carbamazepine is that it causes relatively few cognitive and dysmorphic side effects. Its disadvantages are its unavailability in parenteral formulation and its metabolic autoinduction. The latter must be compensated for by planned dosage increases to maintain therapeutic plasma steady-state levels during the first 2 or 3 months of treatment. Carbamazepine is judged a drug of choice in the treatment of these secondarily generalized tonic-clonic seizures, and the drug of choice in children, adolescents, and women susceptible to the dysmorphic side effects associated with other anticonvulsant agents.     

Etiologic and Preventive Aspects of Epilepsy in the Child–Bridging the Gap Between Laboratory and Clinic

Summary: Four broad categories of basic phenomena are pertinent to developing ways to prevent epilepsy. These include mechanisms of epileptogenesis, ictal initiation and temporary entrainment by the seizure discharge of normally functioning brain, seizure propagation, and control mechanisms that function both to restrain the cascade of epileptic events culminating in a seizure and to arrest the epileptic event and restore the interictal state. In newborns and children, hypoxia-ischemia is a major factor leading to epileptogenesis, and several schemes are proposed to classify, quantify, and prevent hypoxic-ischemic encephalopathy. Control mechanisms must be better understood in order to develop prophylactic recommendations for epilepsy, and an experimental model of "kindling antagonism" may increase our understanding of these. Programs of prevention of seizures in children will evolve only if basic researchers and clinicians work productively together to develop an adequate understanding of factors important in epileptogenesis and antiepileptogenic control mechanisms.     

Predisposing and Causative Factors in Childhood Epilepsy

Summary: We review information from large studies of defined populations, examining the role of known factors and especially of prenatal and perinatal factors in contributing to nonfebrile seizure disorders of early childhood. We depend especially, but not exclusively, on the recently completed analyses from the Collaborative Perinatal Project of the National Institute of Neurological and Communicative Disorders and Stroke, the NCPP. About 4% of children in the NCPP who had at least one non-febrile nonsymptomatic seizure by the age of 7 years had a previous seizure during acute neurologic illness, such as meningitis or during the acute illness after trauma. Many such seizures should potentially be preventable. Of children with seizures, 10% had had a neonatal seizure and 13% had had a febrile seizure. Among the hundreds of prenatal and perinatal factors explored as predictors of childhood seizure disorders, the principal predictors identified were congenital malformations of the fetus, cerebral and noncerebral; family history of certain neurologic disorders; and neonatal seizures. In agreement with the British National Child Development Study, labor and delivery factors in the NCPP appeared to contribute very little to childhood seizure disorders. Maldevelopment, rather than damage at birth to an initially intact nervous system, appeared to be the more common mechanism. Most seizure disorders of early childhood remained unexplained by the large set of prenatal and perinatal characteristics examined.     

Anticonvulsant Drugs and Cognitive Function: A Review of the Literature

Summary: Alterations of cognitive function are separate from disturbances of behavior seen in association with epilepsy. The nature of the cognitive disability may to a certain extent depend on the seizure type. Partial seizures, mainly derived from a temporal lobe focus, impair memory tasks, while generalized seizures seem to have more effect on attentional abilities. A number of studies, reviewed in this paper, suggest that anticonvulsant drugs further impair cognitive function. Maximal impairments are seen in patients receiving polytherapy: rationalization of polytherapy improves cognitive abilities. Studies in children and adults have allowed differentiation of the effects of various commonly used antiepileptic agents. Maximal cognitive deficits are seen with. phenytoin, while phenobarbital and sodium valproate induce moderate disturbances, and carbamazepine seems relatively free from such toxicity. Further research is needed on the interrelationship between types of seizure disorders, types of anticonvulsant medications, and cognitive function.     

Effects of NMD A- and AMPA-Receptor Antagonists on Different Forms of Epileptiform Activity in Rat Temporal Cortex Slices

Summary: Lowering extracellular magnesium induces different patterns of epileptiform activity in rat hippocampus and entorhinal cortex. Short recurrent epileptiform discharges in the hippocampus are stable over time, whereas seizurelike events (SLEs) in the entorhinal cortex, the subiculum, and the neighboring neocortex develop into late recurrent discharges which are not blocked by clinically employed antiepileptic drugs. We tested the sensitivity of the different epileptiform discharge patterns to. /V-methyl-D-aspartate (NMDA)- and non-NMDA-receptor antagonists. As NMDA-receptor antagonist we used dextrorphan, ket-amine, and 2-aminophosphonovalerate (2APV); as α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA)-receptor antagonist we employed the quinoxaline derivative glutamate 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). The findings show that the different patterns of epileptiform activity, including the late recurrent discharges, are sensitive to all NMDA-receptor antagonists. However, when dextrorphan was employed to suppress seizure-like events, later recurrent discharges did not develop during the remaining time course of the experiment. CNQX reversibly suppressed recurrent discharges in the hippocampus and SLEs in the entorhinal cortex. However, late recurrent discharges become insensitive to CNQX, even at a high concentration of 60 μM m. This finding suggests a prominent role for NMDA receptors in the generation of late recurrent discharges.     

The influence of comorbid depression on seizure severity

PURPOSE: To determine the relation between depressive symptoms and seizure severity among people with epilepsy. METHODS: A postal questionnaire was used to survey a nationwide community sample about seizures and depression. The Seizure Severity Questionnaire (SSQ) assessed the severity and bothersomeness of seizure components. The Centers for Epidemiological Studies-Depression scale categorized levels of depression. RESULTS: Respondents categorized as having current severe (SEV, n = 166), mild-moderate (MOD, n = 74), or no depression (NO, n = 443) differed significantly in SSQ scores (all p < 0.0001). People with SEV or MOD reported significantly worse problems than did those with NO depression for overall seizure recovery (mean, 5.3, 4.9, 4.5, respectively); overall severity (5.0, 4.5, 4.2); and overall seizure bother (5.3, 4.8, 4.4) (all p < 0.005). Cognitive, emotional, and physical aspects of seizure recovery also were rated worse among people with SEV than with NO depression (all p < 0.05). Symptoms of depression were significantly correlated with higher levels of all components of generalized tonic-clonic seizure severity (r = 0.33-0.48; all p < 0.0001), and partial seizures (r = 0.31-0.38; all p < 0.01). CONCLUSIONS: Clinically depressed people with epilepsy reported higher levels of perceived severity and bother from seizures, as well as greater problems with overall seizure recovery than did nondepressed people experiencing similar types of seizures. The pervasive influence of depressive symptoms on reports of seizure activity suggests that people with epilepsy should be screened for depression. These data highlight the importance of detecting and treating depression among people with epilepsy.     

Une phénoménologie de la dépendance à l'alcool. Une expérience primordiale de la « nostrité »

The phenomenological approach to alcoholism interestingly focuses on specific dynamics of interpersonal relationships displaying the founding of the Self from a primary “us” and its original basis in the human feast. Priorities for treatment intervention recommend to involve social setting and relationships of the patients, reaching their active participation to a motivational and long term group treatment, underlying the specific therapeutic effect of world exchanges. Biopsychosocial determination of alcoholism could be primarily based on components of interpersonal relationships. Regarding social background, drinking is one of the most famous supports for the achievement of the feast, a founding marker of present time. Taking an existential point of view, the feast appears as the heart of mankind because it presents a primary “us”, a plural state which indicates the beginning and founding of the Self from the others. During the feast, we regularly have to reach our Self from the “us” while avoiding two main dangers, drunkenness, an increase in the dizziness of upright verticality, and addiction, an opposite vertical surrender to alcohol and falling into in the alcoholic relapse, both situations imply a spatial domination and the disappearance of others. Treatment programs of alcohol addicts need to integrate the necessity of reaching the existential basic trust from the support of a group to the appropriation of the community which can be defined as an original “usness”.