养血清脑颗粒治疗卒中后抑郁的疗效及对脑白质结构改变的影响

目的利用磁共振弥散张量成像(DTI)技术,观察养血清脑颗粒治疗卒中后抑郁(PSD)的疗效差异,以及其对脑白质结构改变的影响。方法给予卒中后抑郁患者养血清脑颗粒4 g,口服,3次/d;疗程12 w,治疗前、后均收集汉密尔顿抑郁量表评分(HAMD-24)、DTI扫描数据。治疗后HAMD-24≤8分纳入治愈组,反之纳入难治组。比较两组治疗前、后FA值变化情况。结果养血清脑颗粒治愈率约44.6%。与治疗前相比,治愈组的左侧额叶FA值治疗后明显升高(P0.05);比较两组治疗前的FA值,发现难治组左侧额叶、右侧海马的基线FA值低下(P0.05)。结论养血清脑颗粒治疗PSD有效。PSD患者存在可逆性前额叶深部白质损伤;且难治性PSD患者左侧额叶、右侧海马的基线FA值低下,提示DTI可作为抗抑郁疗效评估的预测指标。     

卒中后抑郁患者血浆P物质水平的研究

目的 通过卒中后抑郁(PSD)P物质(SP)的变化及相关因素研究,探讨PSD与SP的关系.方法 从初次脑卒中后2-4周患者中选取卒中后抑郁(PSD)组46例和卒中后无抑郁组(对照组)45例,前者符合中国精神障碍分类与诊断标准第3版(CC-MD-3)抑郁症的诊断标准.用美国国立卫生研究院卒中量表(NIHSS)进行神经功能评分,汉密顿抑郁量表(HAMD)进行抑郁程度评估,根据卒中24 h后首次CT/MRI结果进行卒中病灶定位,检测血浆SP水平,分析神经功能评分、抑郁程度、卒中部位与血浆SP水平的关系.结果 PSD组血浆SP水平[(58.47±14.39)mg/L]较对照组[(36.98±9.49)mg/L]高(P＜0.001),前者NIHSS评分[(6.83±3.85)]高于后者[(5.04±2.62)],差异有统计学意义(P＜0.05);PSD组血浆SP水平与HAMD评分、NIHSS评分正相关(r=0.83,P＜0.001;r=0.798,P＜0.001);前部卒中组HAMD评分[(3.25±1.90)]、血浆SP水平[(38.45±12.23)mg/L]、NIHSS评分[(9.08±8.72)]较后部卒中组[(6.91±3.30)、(51.21±16.27)、(17.46±15.96)]高(P＜0.05).结论 血浆SP水平增高与PSD有关,可能参与PSD的发生发展过程.     

脑卒中后抑郁合并认知损害的磁共振扩散张量成像研究

目的 探讨脑卒中后抑郁(PSD)合并卒中后认知功能损害(PSCI)患者的磁共振扩散张量成像(DTI)表现及脑卒中后抑郁合并认知功能损害的发病机制。方法 选取武汉大学中南医院2014年10月～2015年12月首发急性脑卒中患者52例,进行汉密尔顿抑郁量表(HAMD)、简明精神状态检查量表(MMSE)、蒙特利尔认知评估(MoCa)量表评分,分为PSD合并PSCI组13例(A组),PSD组(B组)11例,PSCI组(C组)12例,单纯脑卒中组16例(D组)。进行磁共振平扫及DTI扫描,比较各组不同部位FA值的差异。结果 A组与D组比较,双侧额叶、双侧半卵圆中心、左侧颞叶、左侧丘脑、右侧壳核FA值减低,差异有统计学意义(P<0.05)。结论 PSD合并PSCI患者可能具有相对独立的发病机制,与双侧额叶、双侧半卵圆中心、左侧颞叶、左侧丘脑及右侧壳核损害有关。     

脑梗死后锥体束华勒变性的弥散张量成像

目的 应用弥散张量成像(DTI)探讨脑梗死后锥体束华勒变性(WI))弥散参数的变化规律及其早期变化与神经功能的关系.方法 选取2006年3月至2007年1月收入我院神经内科病房的急性(发病7 d内)脑梗死患者15例,男性13例,女性2例.于发病后7 d内、14 d分别进行DTI检查和美国国立卫生研究院腩卒中评分(NIHSS)、日常生活能力指数(BI)、修正的Rankin评分(mRS)、运动功能指数(MI)等神经功能评分.用西门子Trio 3.0T MR机采集DTI数据,由DTI Studio软件处理分析数据.计算出平均弥散系数(MD)、部分各向异件(FA)、第一本征值(λ1)、第二本征值(λ2)和第三本征值(λ3)的参数图.结果 发病14 d时的神经功能评分,NIHSS:6.93±3.39,BI:45.33±26.01,mRS:4.33±0.90,MI:69.47±60.71.发病14 d时病灶侧与健侧DTI指标比较,从大脑脚到延髓各个感兴趣区,脑桥中部的MD和延髓上部的MD两侧差异无统计学意义,其余病灶侧与健侧差异均有统计学意义.病灶侧的MD较健侧下降,病灶侧的FA较健侧减小,λ1较健侧降低,λ2和λ3较健侧增加.发病后14 d的DTI指标与NIHSS呈负相关(r=-0.613,P=0.015),与BI呈正相关(r=0.530,P=0.042),与MI呈正相关(r=0.543,P=0.036).结论 DTI可以检测脑梗死后第2周的脑桥锥体束WD,其表现为λ1下降、λ2和λ3升高、FA降低,尤其是后者与运动功能障碍相关.     

磁共振弥散张量成像研究脑桥梗死后神经纤维华勒变性及临床意义

目的 采用磁共振弥散张量成像(diffusion tensor imanging,DTI)动态观察脑桥梗死后,远离梗死灶的延髓及小脑中脚神经纤维华勒变性及其对患者神经功能恢复的影响.方法 选择单侧脑桥梗死患者14例,以及年龄性别相匹配的健康志愿者14名作对照组.分别在发病第1、4、12周进行DTI检测,并行美国国立卫生研究院卒中评分(National Institutes of Health stroke scale,NIHSS)、简式Fugl-Meyer运动功能评分(Fugl-Meyer motor scale,FM)、共济失调评分(ataxia rating scale,ARS)和Barthel生活指数(Barthel index,BI)评分.结果 与对照组比较,患者梗死灶同侧延髓及双侧小脑中脚的部分弥散各向异性值(fractional anisotropy,FA)从第1周至第12周逐渐减少(延髓梗死同侧FA值:第1周0.43±0.01;第4周0.37±0.02;第12周0.30±0.02,小脑中脚梗死同侧FA值:第1周0.50±0.02;第4周0.43±0.02;第12周0.35±0.04,小脑中脚梗死对侧FA值:第1周0.54±0.02;第4周0.52±0.03;第12周0.47±0.04,t=1.92～28.56,均P＜0.05),而平均弥散量(mean diffusivity,MD)的变化差异却无统计学意义(P＞0.05).在观察期间,患者梗死灶同侧延髓及双侧小脑中脚的FA值减少的百分数绝对值与同期NIHSS及BI变化的百分数绝对值呈负相关(P＜0.05).结论 局灶性脑桥梗死后,同侧延髓及双侧小脑中脚神经纤维的华勒变性持续存在,并且可能阻碍患者神经功能的恢复.     

扣带束和钩束的微观结构变化与白质疏松相关性抑郁

目的通过弥散张量成像(diffusion tensor imaging,DTI)技术研究白质疏松(leukoaraiosis,LA)患者扣带束和钩束的白质微观结构改变,并探讨其与抑郁障碍的关系。方法前瞻性纳入60例Fazekas评分为2~3级的LA患者及30例对照组。LA组分为伴有抑郁(n=33)和不伴有抑郁(n=27)2个亚组。所有被研究对象均进行抑郁评估、3.0T头部MRI常规检查及DTI检查。使用PANDA软件处理DTI数据,提取双侧扣带束和钩束的部分各向异性(fractional anisotropy,FA)数值。结果 LA组双侧钩束及扣带束的FA值均显著低于对照组(P0.05);LA伴抑郁亚组双侧扣带束和右侧钩束的FA值显著低于不伴抑郁亚组(P0.05);LA不伴抑郁亚组和对照组双侧扣带束、钩束之间的FA值无显著性差异(P0.05)。双变量相关分析发现抑郁程度与右侧钩束(r=-0.27,P=0.037)、扣带束(左侧r=-0.329,P=0.01;右侧r=-0.259,P=0.046)FA值呈负相关,与左侧钩束FA变化无明显相关性。结论钩束和扣带束白质微观结构变化与LA相关性抑郁存在关联性,但相关程度较弱(r0.4),提示LA相关性抑郁的发生存在多元化的病理生理基础。     

卒中后抑郁患者小脑弥散张量改变的临床研究

目的利用弥散张量成像(diffusion tensor imaging,DTI)探讨卒中后抑郁(post-stroke depression PSD)患者小脑形态结构改变并分析其与抑郁状态的关系。方法将研究对象分为3组(每组20例),分别为卒中后抑郁组(PSD组),卒中后无抑郁组(CONT组)及对照组(NORM组)。利用多模式磁共振成像(包括磁共振常规序列及弥散张量成像)对60例研究对象的小脑各部分体积的改变和各向异性分数(fractional anisotropy,FA)进行检测,并且对每1例研究对象均进行HAMD量表评定,最后对小脑的结构改变与抑郁量表评分之间进行相关性分析。结果 PSD组患者小脑后叶下部的体积和小脑中、下脚的FA值较CONT组及NORM组均有显著降低(P0.05);CONT组与健康对照组小脑各部分的体积和FA值比较无统计学差异(P0.05);PSD组患者小脑后叶下部的体积减小与HAMD评分成显著负相关,相关系数为-0.896,P0.05;同样,PSD组患者小脑中、下脚FA值的降低与HAMD评分均成显著负相关,相关系数分别为-0.704和-0.916,均P0.05。结论 PSD患者小脑形态结构发生了改变且这种改变与抑郁状态呈显著相关性,进而从临床上初步证实了小脑可能参与了卒中后抑郁的发生。     

丘脑梗死后丘脑放射纤维继发变性的磁共振弥散张量成像

目的 应用磁共振弥散张量(diffusion tensor imaging,DTI)技术动态观察局灶性丘脑梗死后丘脑放射纤维的弥散变化,探讨丘脑梗死后,病灶上方的丘脑放射纤维继发性损害的发生发展规律.方法 连续收录首次发病、单侧丘脑梗死患者17例为实验组,选择健康志愿者17例作对照研究.患者分别在发病的第1周(W1)、第4周(W4)和第12周(W12)进行1次DTI检测,对照组进行1次DTI检测.每次DTI检测之前进行美国国立卫生研究院卒中评分(national institute health stroke scale,NIHSS)和Barthel生活指数(BI)以及自订的感觉障碍分级评分(Sensory disturbance rating,SDR)评定.结果梗死灶上方的半卵圆中心部分异向(fractional anisotropy,FA)值随时间延长逐渐减少(W1:0.42±0.02,W2:0.38±0.02,W12:0.34± 0.03,P<0.01),而平均弥散量(mean diffusion,MD)却无明显变化.梗死灶上方的半卵圆中心FA值的变化百分数与NIHSS、和BI的变化百分数无明显相关(P＞0.05),与SDR变化的百分数呈负相关(r＝-0.246,P<0.05).结论 局灶性丘脑梗死可以引起丘脑放射纤维继发性损害,在12周内这种继发性损害逐渐加重,而且还可能阻碍患者感觉功能的恢复.     

脑小血管病患者MR弥散张量成像的改变及其与认知功能障碍的关系

目的探讨脑小血管病(SVD)患者脑部MR弥散张量成像(DTI)的改变及其与认知功能障碍的关系。方法给55例SVD患者进行神经心理学量表检查,评定认知功能状态,以及行常规MRI和DTI检查,观察感兴趣区的各向异性分数(FA)、表观弥散系数(ADC)。对DTI FA值与蒙特利尔认知评估(MoCA)量表评分的相关性用Pearson相关分析。结果本组SVD患者中认知功能正常(NCI)的患者25例,非痴呆认知功能障碍(VCIND)患者30例。与NCI组比较,VCIND组双侧半卵圆中心、丘脑、额叶及左侧尾状核的FA值显著降低(P0.05~0.001);双侧豆状核、右侧尾状核FA值的差异无统计学意义;左侧尾状核ADC值显著增高(P0.05),其他部位ADC值的差异均无统计学意义。Pearson相关分析示,双侧半卵圆中心、额叶及左侧尾状核的FA值与MoCA量表评分呈正相关(r=0.279~0.375,P0.05~0.005)。结论有认知功能障碍的SVD患者额叶及脑白质DTI的FA值明显降低,并与其认知功能障碍程度有密切的关系。     

卒中后抑郁的相关因素分析

目的探讨卒中后抑郁(PSD)的相关因素。方法采用汉密尔顿抑郁量表(HAMD)在卒中后14 d及90 d对300例脑卒中患者进行评分,并据此分为PSD组及非PSD组,对两组间的卒中部位、美国国立卫生研究院卒中量表(NIHSS)评分、改良Rankin量表评分(mRS)及简易精神状态检查表(MMSE)评分进行比较。结果 140例(46.7%)患者发生PSD;卒中灶多发或位于左侧半球、额颞叶及基底节的患者PSD发生率明显高于卒中灶单发、位于右侧半球、顶枕叶及皮质的患者(均P<0.05);PSD组发病14 d时NIHSS评分、发病14 d及90 d时mRS评分明显高于非PSD组(P<0.05～0.01)。结论 PSD发生与多灶性卒中及卒中灶位于左侧半球、额颞叶、基底节区有关;且与卒中后神经功能缺损程度及残疾程度有关。     

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.     

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.     

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.     

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.