首发抑郁症患者静息态MRI脑局部一致性的改变

目的 利用静息态MRI 技术去探索首发抑郁症患者特异脑区的脑功能改变。方法 对符 合抑郁症诊断标准的20 例患者及20 名健康志愿者进行静息态MRI检查,使用静息态MRI局部一致性 （ReHo）分析方法,比较抑郁症组与对照组ReHo 值,发现特异性增高或减低的脑区。结果 抑郁症组 对比对照组,ReHo 增高的脑区有小脑后叶、颞下回、枕中回、舌回、中央后回、中央前回、额上回、顶 叶等;ReHo 降低的脑区有边缘叶、海马旁回、壳核、丘脑、豆状核、额下回、额中回、楔前叶、扣带回等。 结论 静息态MRI 的ReHo 分析方法可能发现抑郁症异常的脑区,为抑郁症发病机制的探索提供帮助。     

年轻人与老年人简单乘法运算之功能磁共振成像研究

目的应用fMRI技术探讨中国青年和老年人群在简单运算任务下脑激活模式及其与行为学之间的关系。方法分别对青年组(19例)和老年组(20例)健康志愿者进行对照任务和简单运算任务下的fMRI检查。结果两组受试者受教育程度(P=0.125)、智力水平(P=0.921),以及完成对照任务(P=0.142)和简单乘法运算任务(P=0.880)之正确率差异无统计学意义,但老年组受试者完成对照任务(P=0.000)和简单乘法运算任务(P=0.005)反应时间明显延长。青年组受试者在任务刺激下可激活右侧缘上回并向顶内沟和颞中上回后部延伸,中央前回和运动前区、前额叶,左侧缘上回并向颞上回后部和角回延伸,顶内沟区域、颞中下回,内侧后扣带回、楔前叶、辅助运动区、海马沟、海马旁回及前额叶内侧;老年组受试者则分别激活右侧缘上回和顶下区域并向颞中上回后部延伸,中央前回和运动前区、前额叶,左侧缘上回和角回并向顶下延伸,中央前回和运动前区、岛叶及前额叶,内侧后扣带回和中央旁小叶、前扣带回及前额叶内侧;两组受试者共激活脑区包括顶下区域、楔前叶、中央前后回和额顶叶网络,以及颞叶、海马旁回、钩回、屏状核和后扣带回等皮质下结构。结论数学事实提取相关网络的主要成分受年龄影响较小,老年人群的任务激活脑区主要向任务相关顶区集中。     

帕金森病患者静息态脑功能局部一致性研究

目的探讨帕金森病(PD)患者静息态脑功能局部一致性(ReHo)的变化。方法采集22例原发性PD患者(PD组)和22名健康对照者(正常对照组)的静息态功能磁共振(fMRI)数据,并进行比较。分析PD患者"开"期和"关"期局部一致性(ReHo)值差异有统计学意义的脑区的Re Ho值与PD患者左手对指改善率的相关性。结果与正常对照组比较,PD组"关"期ReHo值的减少主要集中在左侧壳核、双侧小脑半球,而增加的脑区集中在右侧丘脑、左侧额中回、左侧运动前区、右侧顶下小叶、右侧中央后回、双侧辅助运动区、楔前叶。PD组患者"开"期双侧小脑、颞下回、右侧壳核、右侧楔前叶、右侧丘脑、双侧辅助运动区ReHo值较"关"期显著增加;而右侧小脑后叶、右侧颞中回、右侧颞上回、左侧额中回、左侧额上回、右侧后扣带回较"关"期显著。PD患者左手对指改善率为1.59%~126.67%,平均(54.15±38.02)%。Pearson相关性分析结果显示,PD患者右侧丘脑ReHo值与左手对指改善率呈正相关(r=0.637,P0.01)。结论 PD患者静息态脑功能存在广泛异常,左旋多巴对于PD患者的大脑功能环路具有修饰作用。丘脑作为运动环路的一个重要节点,在PD患者中其神经元代谢、功能等也发生了改变。     

基于ReHo方法的精神分裂症患者攻击行为的静息态fMRI研究

目的 通过相关脑区结构与功能的对照研究,探讨精神分裂症患者暴力攻击行为的神经认知障碍基础.方法 对有、无攻击行为的精神分裂症患者和健康对照三组人群各21例进行静息状态下脑功能性磁共振成像（fMRI）,运用局域一致性（ReHo）分析方法进行数据分析处理,比较三组之间的差异.结果 与健康对照组相比,精神分裂症非攻击组在左侧额叶、中央前回、中央后回、两侧丘脑、右侧脑岛等脑区的局部一致性存在异常;而精神分裂症攻击组除表现上述脑区局部一致性异常,还表现出两侧前扣带回、左侧海马旁回等边缘系统脑区局部一致性的异常.结论 额叶、丘脑、中央前回、中央后回及脑岛等脑区的异常可能与精神分裂症症状以及攻击行为均有关,而边缘系统等脑区的异常可能与精神分裂症的攻击行为存在特异性联系.     

短暂性脑缺血发作患者脑默认状态网络连通性的改变

目的 探讨短暂性脑缺血发作(TIA)患者脑默认状态网络(DMN)连通性的改变.方法 对16例发作间期TIA患者和16名正常对照者进行功能MR检查,以扣带回/楔前叶及腹侧扣带前回/内侧前额叶作为感兴趣区(ROI),提取ROI内部平均时间信号,分析与ROI连通脑区的功能连通性.结果 与正常对照组比较,TIA组DMN功能连通性减弱的脑区有左侧扣带前回及海马,右侧额前回、岛叶、楔前叶及顶下小叶;功能连通性增强的脑区主要存在于右侧小脑、丘脑及尾状核.结论 TIA患者脑DMN异常,部分脑区的功能连通性减弱;而丘脑、小脑功能连通性增强可能是脑的代偿或保护性反应.     

抑郁症患者对正性面部表情功能识别

目的：利用任务态功能核磁共振成像技术,初步探讨抗抑郁治疗对正性情绪识别脑区功能的影响。方法：检测19例抑郁症患者治疗前和治疗10周后在识别正性及中性面部表情视频时的激活脑区,并与19例匹配的健康者对照比较。结果：与正常对照组相比,治疗前抑郁症患者左右颞上回（BA39）、左后扣带回（BA23）、右后扣带回（BA30）、左丘脑、右岛叶（BA13）等脑区激活显著降低;治疗后患者左颞上回（BA39）、右颞上回（BA22）、左颞中回（BA37）、左右海马旁回（BA30）、右后扣带回（BA29）、右梭状回（BA36）、左额中回（BA8）、右额下回（BA47）、左顶下小叶（BA40）、右岛叶（BA13）等脑区激活较治疗前增强;但与正常组相比,左颞上回（BA22）、左额中回（BA10）、左梭状回（BA20）、左楔叶（BA19）、右顶上小叶（BA7）、右岛叶（BA13）等脑区激活仍存在一定程度的降低。结论：经抗抑郁治疗,抑郁症患者正性情绪识别脑区功能较治疗前有所改善,但与正常对照组相比,仍存在一定程度的功能损害。进一步证实了积极有效的抗抑郁治疗能够部分逆转正性情绪相关脑区损害。     

痉挛性斜颈肉毒毒素治疗前后脑功能磁共振成像研究

目的 应用脑功能磁共振成像(functional magnetic resonance imaging,fMRI)技术,观察痉挛性斜颈(torticollis,idiopathic cervical dystonia,CD)患者行对指动作时的脑激活模式及肉毒毒素局部肌内注射前后的变化,探讨CD可能的发病机制和肉毒毒素治疗后的中枢水平改变.方法 采用fMRI组块设计,分别获得CD患者11例于接受肉毒毒素局部注射前、后4周以及性别年龄匹配的健康志愿者11名执行复杂对指动作任务时的有效脑功能激活图.比较患者治疗前、后与健康对照组的激活差异;以多伦多西方CD等级量表(TWSTRS)评价并比较患者治疗前后症状严重度.分析肉毒毒素治疗所致脑激活水平变化与临床症状评分改变的相关性.结果 CD患者行头扭转同侧对指动作时,同侧壳核、同侧前额叶皮质、对侧初级体皮质等处激活较健康对照明显减低,而同侧楔前叶、同侧梭状回处激活增高.经肉毒毒素治疗后4周CD患者脑内激活水平较健康对照仅对侧楔前叶处减低,其余脑区差异无统计学意义.经肉毒毒素治疗CD患者TWSTRS评分减低,由治疗前(20.02±5.52)分降至治疗后(4.11 ±4.34)分,其差异有统计学意义(t=11.71,P=0.000).肉毒毒素治疗前后脑激活水平变化在下列脑区与TWSTRS评分改变呈正相关:头扭转方向同侧初级体感皮质、前运动皮质、辅助运动皮质、岛叶、梭状回、海马及海马旁回,对侧颞中回、海马及海马旁回等.结论 CD患者存在皮质及皮质下的广泛脑内激活模式异常,可能与感觉运动整合功能紊乱有关,且受累肢体于临床症状出现前可能已处于“预痉挛”状态.肉毒毒素局部注射后CD患者脑内激活模式趋于正常,其机制可能为大脑皮质的功能重塑.     

基于功能连接的复发缓解型多发性硬化患者默认网络静息态功能磁共振成像

目的 采用静息态功能磁共振成像(rs-fMRI)基于种子点相关性分析技术对复发缓解型多发性硬化(RRMS)患者默认网络的功能连接改变进行研究.方法 使用3.0T磁共振采集RRMS组和健康对照组(各27例)rs-fMRI数据.数据经预处理后,选择后扣带回(-5,-49,40)为种子点,采用基于种子点相关性分析技术进行功能连接分析,分别在默认网络内和默认网络外脑区比较两组功能连接的差异.分析差异脑区与临床参数如临床扩展残疾量表、同步听觉连续加法测验评分(PASAT)、脑实质分数、T2可见病灶数和病程的相关性.结果 基于种子点相关性分析技术构建的RRMS患者默认网络包含脑区主要有前额叶皮质腹侧、双侧顶下叶、后扣带回及楔前叶等脑区.在默认网络内比较,RRMS患者较健康对照组右侧额上回功能连接下降;右侧小脑后叶、右侧小脑脚、右侧颞中回、右侧额中回、左侧楔前叶及扣带回、右侧角回、右侧扣带回功能连接增高.RRMS患者组默认网络内差异脑区中,右侧颞中回功能连接系数(0.387±0.216)与PASAT呈负相关(r=-0.590,P =0.001);患者右侧额上回功能连接系数(0.039±0.293)与病程之间呈负相关(r=-0.390,P=0.041).在默认网络外比较,RRMS组后扣带回功能连接下降脑区有右侧额上回、左侧枕中回、左侧中央前回;功能连接增高脑区有右侧小脑前叶(含齿状核)、右侧额叶白质区.RRMS组后扣带回与左侧中央前回、右侧小脑前叶功能连接系数(-0.924±0.253和0.217±0.208)分别与病程之间存在正相关(r =0.650,P=0.000;r =0.436,P=0.023).结论 RRMS患者默认网络内和默认网络外均出现后扣带回静息态功能连接的异常改变,表明患者存在功能下降和代偿的复杂过程.RRMS患者存在有限功能重构或重组,以维持默认网络的功能稳定.     

抑郁症首次发作患者情绪偏向任务的脑功能磁共振成像研究

目的 研究抑郁症首次发作(以下简称首发)患者对不同性质情绪线索的差异脑激活反应,以探讨抑郁症患者"负性情绪偏向性"的脑活动特征.方法 14例抑郁症首发患者与14名配对健康对照者,接受国际情绪图片系统中正性-中性-负性三组图片刺激的脑功能磁共振成像(fMRI)扫描,任务为组块设计;以文拉法辛(75～150 mg/d,口服)治疗患者,随访12周;以汉密尔顿抑郁量表(HAMD17)减分率评估疗效;用神经功能影像分析(AFNI)软件处理影像数据.结果 (1)文拉法辛治疗8周时有效率为58%;12周时有效率为92%,HAMD17总分减分率为60%.(2)两组均激活的脑区包括双侧额中回、双侧背外侧前额叶皮质、左侧丘脑、双侧岛叶、双侧颞叶、双侧杏仁核和海马.(3)在正性/中性图片激活的脑区中,患者组双侧额中回(右侧0.11%,左侧0.09%)及左侧丘脑(0.31%)激活强度均低于对照组(分别为0.98%,1.17%和1.32%;P＜0.05);左侧岛叶(1.03%)及双侧杏仁核(右侧0.47%,左侧0.11%)的激活强度高于对照组(分别为0.45%,-0.34%和-0.49%;P＜0.05).对于负性图片,患者组左侧额中回(2.77%)、左背外侧前额叶皮质(0.18%)、左侧岛叶(1.36%)、左侧颞叶(0.33%)和右侧杏仁核(0.44%)的激活强度高于对照组(分别为1.91%.-0.32%.0.91%,-0.31%,-0.29%;P＜0.05);患者组左侧丘脑激活强度(-0.79%)低于对照组(1.15%;P＜0.05).(4)治疗后,对于正性图片,患者组左侧、右侧额中回及左侧丘脑激活增加为1.21%,1.14%及1.23%(P＜0.05).对于负性图片,左侧额中回(2.05%)、左外侧前额叶皮质(-0.42%)及左侧岛叶(0.73%)的激活降低(P＜0.05);左侧丘脑(1.53%)激活增加(P＜0.05).结论 前额叶、左侧岛叶、左侧颞叶、杏仁核和左侧丘脑对不同性质情绪诱导线索的异常激活,与抑郁症首发患者偏向性情绪障碍相关;文拉法辛对前额叶、左侧岛叶和丘脑的异常激活有调节作用.     

精神分裂症患者基于事件前瞻记忆缺陷的功能磁共振成像特点

目的应用功能磁共振成像(fMRI)技术探讨精神分裂症基于事件前瞻记忆缺陷的生物学基础及神经机制。方法采取横断面病例对照研究方法,共招募20名健康志愿者(对照组)和20例精神分裂症患者(观察组)入组,以双重任务前瞻记忆实验范式作为刺激任务,同时应用阳性与阴性症状量表和阴性症状评定量表评定精神症状严重程度,采用锥体外系不良反应量表评定锥体外系不良反应严重程度。应用Matlab2011b,SPM8软件对影像学数据进行预处理及统计分析。采用独立样本t检验分析比较两组的脑区激活情况,设定激活差异显著水平为P<0.005(未校正)。选取前瞻记忆主要激活脑区,应用REST1.8软件提取激活脑区的血氧水平依赖性信号强度,采用Pearson相关分析探究脑区激活强度的相关因素。结果预处理中发现,观察组2例被试者有明显的头部运动(移动>2.5 mm,转动>2.5°),剔除图像分析,最后观察组18例,对照组20例被试者的图像数据进入统计分析。相对于健康志愿者,精神分裂症患者在执行前瞻记忆任务时的正确率较低且反应时更长[(83.40±15.33)%比(94.30±10.94)%,(870.54±156.70)ms比(757.33±187.44)ms;均P<0.05]。进行中任务的反应时与阴性症状量表评分呈正相关(r=0.494,P=0.037),前瞻记忆任务的正确率与智商呈正相关(r=0.558,P=0.016),前瞻记忆任务的反应时与氯丙嗪等效剂量呈正相关(r=0.492,P=0.038)。fMRI扫描显示精神分裂症患者右额中回、双侧顶下小叶(角回、缘上回)、右前扣带回以及右楔前叶脑区激活明显低于健康志愿者(均P<0.005)。右缘上回(r=-0.589,P=0.010)、左角回(r=-0.593,P=0.010)、右楔前叶(r=-0.590,P=0.010)的激活程度与氯丙嗪等效剂量呈负相关。右前扣带回(r=-0.537,P=0.021)、右额中回(r=-0.501,P=0.034)的激活程度与进行中任务的反应时呈负相关。结论前瞻记忆需要消耗认知资源。精神分裂症患者存在显著的基于事件前瞻记忆缺陷,其缺陷机制可能与额中回、顶下小叶(缘上回、角回)、前扣带回以及楔前叶功能紊乱有关。     

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.     

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.     

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.     

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.     

Pediatric Epilepsy Surgery

Summary: The use of implantable arrays of epidural electrodes has made it possible to carry out extraoperative electrocorticography (ECoG) and functional localization in the awake child. This has permitted cortical excisions that are determined by criteria similar to those obtained during surgical procedures performed under local anesthesia in adults. In addition, the method also permits simultaneous ECoG and video monitoring during the child's symptomatic seizures, providing additional important localizing information that is impractical to obtain in operations under local anesthesia. We report our experience with 75 children, ages 5 months to 15 years, whom we have managed with epidural electrode arrays. The method of extraoperative ECoG is described and illustrative cases are presented to demonstrate its feasibility and utility in children. In addition, we call attention to gliomas as a common cause of chronic focal seizures in children. Of 49 children undergoing resection and followed for from 1 to 14 years (mean of 5.8 years), 32 (65%) are either seizure free or have had a significant reduction in seizure frequency that has unambiguously improved their quality of life. The results are analyzed further by relating the surgical outcome to each of the pathologic entities that caused the seizures. This analysis reveals the variety of neurological conditions that commonly cause intractable focal seizure disorder in children and distinguishes those pathologic entities in which the seizure disorder is apt to respond to surgical intervention from those that will not.     

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.