抑郁症患者脑白质变化初步研究

目的：利用能够提示脑白质纤维完整性的磁共振弥散张量成像（DTI）探讨首发和复发重性抑郁症患者脑白质纤维的变化及其差异。方法：20例重性抑郁症患者（首发9例，复发11例）和20名正常对照者均经常规磁共振成像（MRI）平扫，未发现异常者继续进行DTI和结构MRI（3D）扫描，基于像素的全脑分析技术对DTI数据进行分析。结果：与对照组相比较，抑郁症组白质纤维结构在双侧额中回、右顶下小叶及双侧脑岛等区域白质的各向异性值（FA）显著降低（各脑区P均〈0.001，cluster〉30像素）;与首发抑郁症患者相比较，复发抑郁症患者右侧额上回、右顶叶、中央前回、中央后回及右顶下小叶等区域FA值降低更为显著（各脑区P均〈0.001，cluster〉10像素）。结论：重性抑郁症患者存在脑白质异常，抑郁反复发作会导致脑白质损害进一步加重。     

老年抑郁症首次发病与复发患者脑结构的磁共振研究

目的:基于磁共振探讨首发与复发老年抑郁症患者脑结构特点。方法:对首发与复发老年抑郁症患者30例(首发组20例,复发组10例)和正常人30名(正常对照组)进行脑磁共振成像检查并运用弥散张量成像(DTI)扫描,比较首发与复发抑郁症患者与正常对照组的异常脑区以及首发与复发患者脑白质、灰质容量及白质各向异性分数(FA)值的差异。结果:与正常对照组比较,患者组双侧额叶、右顶叶、左楔叶、左海马回灰质以及左颞上回白质T1信号强度减低;右扣带回灰质T1信号及白质T1信号强度升高(P0.01,像素集合30)。首发组和复发组患者脑白质容量未发现显著差异脑区,但复发组右海马区灰质容量较首发组明显减小(P0.01,像素集合30)。与首发组比较,复发组右额中回、左颞中回白质FA值减低(P均0.01,像素集合30)。结论:首发与复发老年抑郁症患者可能存在前额叶及右扣带回功能缺陷;双侧海马区灰质容量可能与临床症状有关。     

创伤后应激障碍患者脑结构的磁共振研究

目的探讨创伤后应激障碍（PTSD）患者是否存在大脑结构形态学的改变。方法对12例因火灾事故而致PTSD患者（PTSD组）、12名年龄、性别和创伤暴露均与PTSD组相匹配的正常人（对照组）进行MRI扫描，获取脑结构的T1加权像和3维图像，进行基于像素的形态测量学分析，比较两组灰质、白质密度的异同。结果在控制了年龄和性别的影响后，PTSD组与对照组灰质密度比较的差值，在左侧海马（Talairaeh坐标：x=-26mm，y=-13Inln，z=-17mm，t=5．05）、左侧前扣带回（X=-2mm，y=40mm，z=17mm，t=5．06）和双侧岛叶（右侧岛叶x=34mm，y=4mm，z=6mm，t=4．64；左侧岛叶x=-34mm，y=4mm，z=6mm，t=4．44）的差异有统计学意义（P〈0．001）；两组在其他脑区灰质或白质密度的差异无统计学意义。结论创伤后应激障碍患者的海马、前扣带回和岛叶都有灰质密度的减少，提示这些脑区的结构存在病理性改变。     

精神病未治疗期对首发未服药精神分裂症脑白质完整性的影响

目的 探讨精神病未治疗期(DUP)对首发未服药精神分裂症患者脑白质完整性的影响.方法 应用汉化的诺丁汉发病症状量表评定39例首发未服药精神分裂症患者的DUP,以其中位数为界将患者分为长DUP组和短DUP组,同时比较两组患者的性别构成、年龄、受教育年限、阳性和阴性症状量表总分.采用自旋回波序列得到弥散张量磁共振成像资料,以DTI-Studi0软件和统计参数图软件(SPM5)对所得图像进行预处理,得到的分子各向异性分数(FA)图像在SPM5软件中进行两样本t检验,获得两组FA差异统计参数图.结果 两组患者性别构成、年龄、受教育年限、阳性和阴性症状量表总分比较差异无统计学意义(P＞0.05).在P值小于0.001(未校正)水平下,长DUP组患者大脑右侧前扣带束(x=8,y=40,z=24)和左侧前额叶白质(x=32,y=34,z=4)FA值较短DUP组降低.结论 延长的DUP会降低首发未服药精神分裂症患者脑白质的完整性.     

精神分裂症早期的脑白质和灰质信号强度下降

目的分析精神分裂症早期阶段脑灰质和脑白质结构的变化。方法对25例早期阶段(病程小于6个月)的首发未用药的精神分裂症患者和28名正常对照的脑部进行磁共振T1加权成像,所得图像以统计参数图软件包进行预处理,再对两组脑灰质密度和白质信号强度进行t检验。结果患者组左侧岛叶区(x=34,y=18,z=-2,体素集合数=163)、左枕叶(x=14,y=-66,z=14,体素集合数=76)、右侧额叶(x=46,y=44,z=8,体素集合数=74)白质信号强度较正常对照组降低(t=-3.78,P=0.007;t=-3.36,P=0.02;t=3.26,P=0.03);右侧枕叶(x=10,y=-84,z=8,体素集合数=64)脑灰质信号强度比正常对照组降低(t=3.12,P=0.03)。结论精神分裂症早期阶段即存在脑实质结构异常,以白质为著。     

首发未服药精神分裂症患者脑弥散张量成像的基于体素分析

目的分析首发未服药精神分裂症患者脑白质完整性的变化。 方法对40例首发未服药精神分裂症患者和68例健康对照者进行脑弥散张量磁共振成像检查,以DTI-studio软件和统计参数图(SPM)软件对所得图像进行预处理,得到的各向异性分数(FA)图像在SPM软件中进行两样本t检验,获得两组患者FA值差异统计参数图。 结果在P值小于0.001（未校正）水平下,首发未服药精神分裂症患者右侧杏仁核区(MNI：24,2,-14,cluster=347 voxels)、双侧前扣带区(MNI:6,42,2,cluster=586 voxels)、右侧前额叶眶上回区域(MNI：20,18,-10,cluster= 166 voxels)白质FA值较健康对照者下降,且未发现前者有脑区白质FA值较后者增高。 结论精神分裂症患者皮层一边缘系统环路存在结构连接障碍,这可能是精神分裂症的神经机制。     

未经治疗的抑郁症首次发病患者脑弥散张量成像的研究

目的 通过对未经治疗的抑郁症首次发病(以下简称首发)患者进行弥散张最成像(DTI)检查,探讨抑郁症患者脑门质的完整性及其与病程和抑郁严重程度的相关性.方法 对17名首发末服药抑郁症患者(以下简称患者组)和17名年龄、性别和文化程度相匹配的健康对照(以下简称对照组)进行全脑DTI扫描.以基于体素的分析比较两组受试者脑白质的分数各向异性(FA)的差异.提取差异有统计学意义的脑区的FA绝对值,将其与汉密尔顿抑郁量表(17项,HAMD)总分和患者病程进行相关分析.结果 患者组的双侧额中回、左侧扣带回和颞下回白质的FA值显著低于对照组(P＜0.01,cluster＞100).右侧额中回的FA值与病程呈显著负相关(r=-0.732,P=0.001).未发现各脑区的FA值与HAMD总分存在相关.结论脑白质完整性异常可能是抑郁症的生物学特征之一,抑郁症病程对脑白质的完整性有明显影响.     

有无冲动攻击行为首发精神分裂症脑灰质体积的比较

目的 比较有无冲动攻击行为精神分裂症脑灰质结构的不同.方法 收集16例有冲动攻击行为和24例无冲动攻击行为的首发未用药的精神分裂症患者,以三维快速扰相梯度回波序列获得其脑部磁共振成像.所得图像以统计参数图软件包进行预处理,然后两组脑局部灰质体积进行t检验.结果 有冲动攻击行为组右侧中央前回、中央后回区(MNI:x=44,y=-4,z=58;体素集合数=851)和右侧眶额回区(MNI:x=20,y=34,z:-24,体素集合数=108)脑灰质体积小于无冲动攻击行为组,差异有统计学意义(t=-3.72,P<0.001;t:3.17,P<0.001).未发现冲动攻击行为组存在灰质体积大于无冲动攻击行为组的脑区.结论 右侧中央前回、中央后回和眶额回灰质异常与精神分裂症的冲动攻击行为可能有关.     

首次发病未用药老年抑郁症患者脑白质完整性的弥散张量成像研究

目的 使用弥散张量成像探讨首次发病未用药老年抑郁症患者的脑白质完整性.方法 15例首次发病未用药的老年抑郁症患者和15例正常对照组接受脑弥散张量成像扫描,用基于体素的分析方法对脑内所有体素的各向异性分数(FA)逐一进行组间比较.结果 与正常对照组相比,首次发病未用药老年抑郁症患者左侧前扣带(丛集体积=106体素,t=3.21)、右侧前扣带(丛集体积=60体素,t=2.71)、右侧膝下扣带(丛集体积=63体素,t=3.37)、左侧脑干(丛集体积=62体素,t=3.25)白质FA值显著降低(检验水准为未校正的单侧P＜0.01,体素集阈值＞50体素).结论 老年抑郁症发病早期存在双侧前扣带及右侧膝下扣带白质完整性下降,经由该脑区的神经通路损害可能与老年抑郁症的病理机制有关.     

部分性发作癫痫患者静息状态功能磁共振默认模式网络的功能连接改变

目的 应用静息状态功能磁共振成像(fMRI)探讨部分性发作癫痫患者静息状态下的脑功能改变.方法 对60例部分性发作癫痫患者(患者组)和60名性别、年龄和教育程度匹配的健康对照者(对照组),使用3.0T磁共振采集两组的静息状态下fMRI数据,采用功能连接方法分析计算脑区的默认模式网络的功能连接,利用SPM5软件分析比较患者组和对照组脑功能的差异.结果 患者组的默认模式网络的功能连接主要包括左侧楔前叶/后扣带回和角回、扣带回;对照组的功能连接主要包括左侧楔前叶/后扣带回和右侧角回,双侧内侧额叶和颞叶;患者组的左侧顶下小叶[坐标值(x,y,z):-57,-39,48;t=4.90,P＜0.01]、左侧缘上回[坐标值(x,y,z):-63,- 48,33;t=4.25,P＜0.01]、左侧海马旁回[坐标值(x,y,z):-30,-6,-21;t =4.05,P＜0.01]、左侧颞上回[坐标值(x,y,z):-48,-39,6;t=3.72,P＜0.01],左侧钩回[坐标值(x,y,z):-24,6,- 36;=4.56,P＜0.01]及右侧钩回[坐标值(x,y,z):33,-15,- 36;t=4.00,P＜0.01]的默认模式网络功能连接较对照组降低;未发现功能连接升高的脑区.结论 部分性发作癫痫患者静息状态下脑区的功能连接改变,可能是部分性发作癫痫潜在的病理生理机制.静息状态fMRI能发现常规MRI正常的癫痫患者的广泛脑功能异常,是一种无创的研究癫痫患者脑功能的有效方法.     

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.     

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.     

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.     

Treatment Considerations in Anticonvulsant Monotherapy

Summary: The long-standing practice of polypharmacy in treating epilepsy is giving way to use of monotherapy. Monotherapy can improve seizure control as well as reduce the risk of serious idiosyncratic reactions, dose-related side effects, and complex drug interactions. Monotherapy also offers improved compliance and cost-effectiveness. The basis of monotherapy is accurate diagnosis and assessment of the patient's seizure type(s), followed by selection of a single appropriate anticonvulsant drug. Many patients currently treated with multiple anticonvulsants can be successfully converted to monotherapy with a carefully monitored program in which troublesome and redundant drugs are gradually withdrawn from the therapeutic regimen.     

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.     

Dextromethorphan: Cellular Effects Reducing Neuronal Hyperactivity

Summary: Dextromethorphan is a dextrorotary morphinan without affinity for opioid receptors, commonly used as an antitussive medication. During the past 5 years, interest in the compound and its demethylated derivative, dextrorphan, has been revived because additional neuroprotective and an-tiepileptic properties were found in in vitro studies, animal experiments, and a few clinical cases. Both morphinans are able to inhibit N -methyl-D-aspartate (NMDA) receptor channels and voltage-operated calcium and sodium channels with different potencies. The inhibition of the NMDA receptor is believed to be the predominant mechanism of action responsible for the anticonvulsant and neuroprotective properties of the compounds.     

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.