脑白质疏松伴认知障碍患者静息态功能磁共振成像研究

目的 研究脑白质疏松（leukoaraiosis,LA）伴发认知障碍患者与健康人静息态脑网络的差异。 方法 分别对根据影像学及临床确诊的40例脑白质疏松伴认知障碍患者及30例年龄、性别、受教育 程度均匹配的健康对照者进行静息态功能磁共振扫描,采用独立成分分析法得到两组被试者的激 活区,对两组数据进行比较,得到两组间的激活差异区。 结果 脑白质疏松伴认知障碍患者默认网络中双侧楔前叶、左侧颞下回、左侧枕颞内侧回、右侧前 扣带回激活较正常对照组减弱,左侧中央旁小叶及右侧楔叶激活程度较正常对照组增强。 结论 脑白质疏松伴认知障碍患者与健康人在脑静息网络激活程度上存在差异。     

颈动脉狭窄伴认知功能障碍患者脑默认网络变化

目的利用fMRI对颈动脉狭窄伴认知功能障碍患者的脑默认网络进行观察分析,结合神经心理学测验量表,探讨低灌注状态下脑默认网络连接与认知功能二者之间的联系。方法共纳入2017年6月至2018年12月经DSA证实的16例单侧症状性颈内动脉重度狭窄(狭窄率≥70%)患者为研究对象,分别采用简易智能状态检查量表(MMSE)和蒙特利尔认知评价量表(MoCA)进行认知功能评价,并基于血氧水平依赖性功能磁共振成像建立脑网络模型,比较颈动脉狭窄组与正常对照组受试者功能连接的差异性。结果颈动脉狭窄组患者MoCA评分低于正常对照组[(21.19±4.00)分对(27.94±2.00)分;t=2.609,P=0.048],提示存在一定程度的认知损害。颈动脉狭窄组和正常对照组受试者组内显著功能连接均呈现额叶至枕叶、大脑半球内与双侧大脑半球间广泛分布,但颈动脉狭窄组患者功能连接明显减弱。其中,双侧大脑半球间功能连接减弱以右侧额叶与左侧顶叶、左侧颞叶之间,右侧顶下缘角回与左侧杏仁核之间,双侧楔叶间等脑区为主;大脑半球内则表现为双侧内额叶和前额叶间功能连接减弱。颈动脉狭窄组患者尚可见局部脑区功能连接特异性增强。结论颈动脉狭窄伴认知功能障碍患者在静息状态下脑默认网络可发生改变,在fMRI上呈现大脑半球内及双侧大脑半球间功能连接增强或减弱,可能与长期低灌注引起的局部脑功能改变有关。     

基于功能磁共振成像的早发精神分裂症默认网络研究

目的：探讨早发精神分裂患者在静息状态下脑默认网络功能连接特点。方法：采用功能磁共振成像（fMRI）技术,对26例早发精神分裂症患者和28例正常对照进行静息状态下全脑的磁共振脑功能扫描。采用功能连接分析方法,提取静息状态下默认网络,在患者组和对照组中分别计算默认网络各脑区两两间的功能连接。结果：早发精神分裂症组在默认网络存在5条异常连接。其中3条连接表现为连接增强：腹侧前额叶内侧皮质-右侧颞下回（P=0.0078）,腹侧前额叶内侧皮质-左侧外侧顶叶（P=0.0091）、腹侧前额叶内侧皮质-背侧前额叶内侧皮质（P=0.0163）。2条连接表现为连接减弱：右侧外侧顶叶-小脑扁桃体（P=0.0223）,左侧额上回-右侧下半月小叶（P=0.0294）。结论：早发精神分裂症患者存在默认网络功能的异常。这些异常改变可能与精神分裂症的病理机制相关。     

颞叶内侧癫癎海马功能连接的功能磁共振成像研究

目的研究颞叶内侧癫癎患者右侧海马与全脑,尤其是默认网络功能连接的关系,探讨颞叶内侧癫癎患者默认网络异常的机制及其形成的颞叶癫癎网络。方法23例颞叶内侧癫癎患者,采用静息功能连接的功能磁共振成像,选择右侧海马作为兴趣区,获得正常对照组和颞叶内侧癫癎组受试者的脑功能连接激活图,观察其右侧海马与全脑的功能连接。结果正常对照组受试者默认网络包括海马、后扣带回和（或）楔前叶、前扣带回和（或）前额叶内侧、角回及前颞叶。颞叶内侧癫癎组患者右侧海马与默认网络的正向功能连接明显减弱,与右侧额下回、颞上回及第一运动感觉皮质下部的正向功能连接增强;与前额叶背侧、顶间沟及第一运动感觉皮质上部的负向功能连接减弱。结论在颞叶内侧癫癎患者功能连接网络中,默认网络及部分正向功能连接网络受损,提示患者存在广泛的、与海马相关的生理功能丧失;与右侧额下回、颞上回及第一感觉运动皮质下部的功能连接增强则可能与颞叶癫癎网络有关。     

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.     

修正蒙特利尔认知评估量表评估脑白质疏松症认知功能障碍的效果研究

目的探讨修正的蒙特利尔认知评估量表(MoCA)评估脑白质疏松症认知功能障碍的应用效果。方法选取本院诊治的脑白质疏松症认知功能障碍患者53例为观察组,选取本院同期健康体检人员53例为对照组,均行MoCA和简易精神状态量表(MMSE)评定,比较2组MoCA和MMSE评分结果以及观察组不同严重程度间MoCA和MMSE的评分结果,分析MoCA和MMSE的诊断价值,分析MoCA、MMSE与脑白质疏松症认知功能障碍的相关性。结果观察组MoCA、MMSE量表视觉空间与执行能力评分、命名评分、注意力评分、语言评分、延迟回忆评分、抽象评分、定向力评分、总评分均明显低于对照组。中度认知功能障碍患者MoCA评分、MMSE评分均明显低于轻度认知功能障碍患者,重度认知功能障碍患者均明显低于轻度和中度认知功能障碍患者。MoCA的灵敏度、阴性预测值、约登指数均明显高于MMSE,MoCA的特异度明显低于MMSE,但差异均有统计学意义(P0.05)。MoCA的阳性预测值低于MMSE,差异无统计学意义(P0.05)。MoCA与MMSE具有明显的正相关性,MoCA、MMSE与脑白质疏松症认知功能障碍均具有明显负相关性。结论 MoCA是脑白质疏松症认知功能障碍的有效评估方法,与患者认知功能障碍的严重程度密切相关,灵敏度高,值得临床推广使用。     

静息状态下强迫症突显网络内部异常的功能连接

目的 探讨静息状态下未经治疗的强迫症患者突显网络内部功能连接特点及与临床症状 之间的关系。方法 对20 例未经治疗的强迫症患者和20 名性别、年龄和受教育程度相匹配的健康被试 进行静息态的MRI 扫描，利用DPABI 分析软件，采用基于种子点的功能连接方法分析强迫症患者静息 态突显网络的特点；采用偏相关分析方法探讨强迫症突显网络与临床症状之间的关系。结果 与健康 对照相比，强迫症患者突显网络内部左侧眶额回的功能连接减弱［（0.08±0.09）比（0.27±0.07）；t=-7.80， P＜ 0.001，高斯随机场理论矫正］。结论 静息状态下强迫症患者突显网络内部存在异常的功能连接。 【关键词】 强迫症； 功能磁共振成像； 静息态； 突显网络     

脑小血管病引发的脑白质疏松与认知功能障碍的相关性研究

目的分析脑小血管病引发的脑白质疏松与认知功能障碍的相关性。方法选取脑小血管病伴脑白质疏松患者60例为研究组,另选取无神经系统疾病和精神疾病的60例健康人为对照组,研究组患者进行脑颅MR扫描,根据白质变化分级量表分为Ⅰ度(轻度)亚组20例、Ⅱ度(中度)亚组20例及Ⅲ度(重度)亚组20例,根据简明精神状态量表及蒙特利尔认知量表对认知功能进行评估,探讨脑白质疏松与认知功能障碍的关系。结果脑白质疏松的影响因素有年龄及微出血史(P0.05),与受教育时间、高血压史、糖尿病史及高血脂无明显关系(P0.05);经简明精神状态量表评分,Ⅰ度亚组患者评分(20.5±4.1)与对照组比较(22.5±4.5)无显著差异(t=1.395,P0.05);Ⅱ度亚组和Ⅲ度亚组分别为16.5±3.5、16.0±3.3,明显低于对照组的22.5±4.5(P0.05);经蒙特利尔认知量表明细评分,研究组视空间与执行能力、注意力、语言能力、抽象能力、命名能力、延迟记忆和定向力评分低于对照组(P0.05)。结论脑小血管病引发的脑质疏松与认知功能障碍有重要联系,可通过脑白质疏松情况对患者进行认知障碍的早期检查。     

基于脚桥核神经网络的帕金森病冻结步态的机制探讨

目的探讨脚桥核(PPN)神经网络在帕金森病(PD)冻结步态(FOG)中的作用及其变化规律。方法对16例PD伴冻结步态(PD FOG+)患者,17例PD不伴冻结步态(PD FOG-)患者及17名正常对照者,行静息态功能MRI(rs-fMRI)扫描,并用功能连接方法对结果进行分析;同时行DTI检查,对脑白质纤维DTI的各相关参数进行组间比较。结果与正常对照组及PD FOG-组相比,PD FOG+组与PPN功能连接异常的脑区主要分布在皮质-脑桥核-小脑通路以及视觉相关颞叶皮质;与正常对照组相比,PD FOG+组存在明显的脑白质结构异常改变,包括连接两侧大脑半球的胼胝体、连接皮质-皮质间的白质纤维束、连接皮质-皮质下结构的白质纤维束以及连接丘脑的白质纤维束。结论 PD FOG+患者存在异常的PPN功能连接网络,主要影响皮质-脑桥核-小脑通路和参与视觉信息处理的颞叶相关皮质,并有显著的脑白质结构异常改变,可涉及运动、感觉和认知传导相关通路。如结合rs-fMRI和DTI技术,可以进一步提高对PD FOG潜在发病机制的认识。     

精神分裂症患者基底节功能连接的静息态fMRI研究

目的通过功能磁共振(fMRI)技术,探讨精神分裂症患者静息状态下与基底节异常连接的脑区。方法采用3.0T功能磁共振成像技术检测15例精神分裂症患者与12例正常对照组在静息状态下的全脑功能活动。采用功能连接分析对比两组被试的基底节(双侧尾状核、壳核和苍白球共6个区域)与全脑功能连接的差异。结果与对照组相比,精神分裂症患者的内侧额上回、后扣带与尾状核的功能连接上升;左侧额上回、右侧前扣带与左侧苍白球功能连接上升;左内侧额上回与右侧苍白球功能连接上升;左侧额上回与左侧壳核功能连接上升。差异均有统计学意义。结论精神分裂症患者的基底节区域与默认网络的重要节点功能连接上升,提示基底节-默认网络环路出现异常,这可能与精神分裂症的病理机制有关。     

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.     

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.     

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.     

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.     

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.     

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.     

Special Pharmacokinetic Considerations in Children

Summary: Pediatric patients have greater degrees of pharmacokinetic variability and unpredictability than adults. This variability results from the effects of pharmacogenetics, age and growth, prior and current comedication, and disease. Newborns with seizures have the least predictable dosage requirements, and their needs change as drug-eliminating mechanisms mature in the neonatal period. Infants have the highest relative capacities to eliminate antiepileptics of any age group and require the largest relative doses. In addition to age-related trends, children demonstrate the same drug-specific, pharmacokinetic phenomena that adults do, including nonlinear phenytoin elimination, nonlinear valproate binding, and autoinduction of carbamazepine. Intercurrent illness and drug interactions further modify the age-related pharmacokinetic patterns in children and make dosage requirements even more unpredictable. Recent studies have shown that febrile illness can affect drug elimination, sometimes decreasing drug levels by 50% or more. Intermittent treatment with benzodiazepines administered either orally or rectally can be an important adjunct and help minimize this type of problem for children with marginally controlled epilepsy. Intermittent benzodiazepines are also helpful for children who have febrile seizures and who need only occasional antiepileptic protection.