脑小血管病患者伴发非痴呆血管性认知功能损害情况及尼莫地平疗效的研究

目的探讨脑小血管病(cerebral small vessel disease,SVD)不同亚型伴发非痴呆血管性认知功能损害的情况,评价尼莫地平对SVD的疗效。方法选择SVD患者118例,包括52例腔隙灶脑梗死(LI)和66例白质疏松(WML)患者。分别将LI组和WML组患者随机分组为治疗组(基础治疗加尼莫地平治疗)和对照组(基础治疗),进行6个月治疗。治疗前后对所有患者采用蒙特利尔认知评估量表(MoCA)、简易智能状态检查表(MMSE)、语义分类流畅测验(动物)、Stroop测验(计算错误数)、画钟试验、积木测验、数字广度顺背测验、数字符号测验、逻辑记忆亚测验和再生亚测验进行认知功能评价,并比较各组患者治疗前后认知功能评分。结果治疗前,LI组患者语义分类流畅测验(动物)、数字符号测验、逻辑记忆亚测验、视觉再生亚测验、MoCA、MMSE评分显著高于WML组患者,Stroop测验得分显著低于WML组患者。经过6个月治疗后,LI组和WML组患者中的对照组治疗前后各项认知功能评分均没有统计学差异(P>0.05)。LI组患者中治疗组MoCA、画钟试验和数字广度顺背测验得分升高,Stroop测验得分下降(均P<0.05);WML组患者中治疗组MoCA、MMSE、画钟试验、数字广度顺背测验和视觉再生亚测验得分升高,Stroop测验得分下降(均P<0.05)。结论 SVD两个亚型伴发非痴呆血管性认知功能损害情况不同,LI患者损害程度比WML患者轻。尼莫地平治疗可较好的改善患者的执行功能、视空间结构能力和注意力。     

P300和总脑小血管病评分对脑小血管病患者认知 障碍评估的临床价值

目的 本研究旨在评估 P300、总脑小血管病（CSVD）评分对 CSVD 患者认知障碍程度的 检测作用，并探讨认知功能筛查量表与之匹配程度。方法 纳入 2018 年 10 月至 2020 年 6 月就诊于 连云港东方医院神经内科并诊断CSVD的患者72例，同时纳入同期评价的年龄、性别与之匹配的34名 健康体检者设为对照组。所有纳入者均在一周内检查简易智力状态检查量表（MMSE）和蒙特利尔 认知评估量表（MoCA）和 P300、总 CSVD 评分。CSVD 患者根据认知功能筛查量表（MMSE、MoCA）分 为认知障碍组和非认知障碍组，分析 3 组间 MMSE、MoCA 评分与 P300 潜伏期、P300 波幅、总 CSVD 评分的关系。结果 认知障碍组和非认知障碍组在中央点（Cz）记录的P300 潜伏期均长于对照组 （P＜ 0.001），认知障碍组P300 潜伏期长于非认知障碍组［（397.471±35.911）ms比（342.584±14.502）ms， P＜ 0.001］。认知障碍组和非认知障碍组的总 CSVD 评分高于对照组（P＜ 0.001），认知障碍组总 CSVD 评 分 高 于 非 认 知 障 碍 组（P＜ 0.001）。 相 关 分 析 显 示 MMSE、MoCA 评 分 与 P300 潜 伏 期（r=-0.768， P＜ 0.001；r=-0.824，P＜ 0.001）、总 CSVD 评 分 之 间（r=-0.816，P＜ 0.001；r=-0.896，P＜ 0.001）存 在 强负相关关系。当 P300-Cz 潜伏期为 348.4 ms 时，CSVD 患者诊断认知障碍的敏感度为 94.3%，特异 度为 83.1%。当总 CSVD 评分为 2 分时，CSVD 患者诊断认知障碍的敏感度为 82.9%，特异度 97.2%。 结论 P300 潜伏期、总 CSVD 评分可能是 CSVD 患者认知功能障碍的早期预测指标，且较 MMSE、MoCA 量表可能更客观地反映认知功能     

脑小血管病认知障碍特点及与影像学总负荷评分的关系

目的探讨脑小血管病(cerebral small vessel disease,CSVD)认知障碍特点及与影像学总负荷评分的关系。方法采用横断面调查,纳入2016-10—2019-12中山市中医院就诊的脑小血管病患者272例,以MMSE评分进行分组,同时纳入年龄、性别、受教育程度匹配的健康志愿者30例,采集各组人口学信息及血管病危险因素,磁共振检查评价脑小血管病总体负荷评分,利用MoCA量表评估认知水平。结果 CSVD无认知障碍组118例,认知障碍组154例,2组受教育年限、既往卒中病史方面差异有统计学意义(P<0.05)。各组MoCA总分存在显著差异,认知障碍组视空间及执行功能、记忆、语言、注意、计算方面,评分明显下降(P<0.05)。以总负荷评分对CSVD患者进行分类,总负荷评分1~2分主要分布于无认知障碍(97.46%)和轻中度认知障碍(76.11%)患者,3~4分则主要分布于重度认知障碍(87.80%)患者,差异有统计学意义(P<0.01)。进一步MoCA认知域评价,在总负荷评分≥1分出现视空间及执行、注意下降,当评分≥3分时认知域受累增多,评分明显降低,出现视空间与执行、记忆、语言、注意力、抽象、计算等多个认知域损害(P<0.05)。结论 CSVD相关认知功能障碍以视空间及执行功能受累为特点,随影像学负荷评分增加,认知功能障碍受损加重。     

老年脑小血管病影像学总负担评分与认知功能障碍的相关性分析

目的研究老年人群脑小血管病(CSVD)的神经影像学特征总负担评分与认知障碍的关系。方法选取2016年6月-2019年5月于辽宁省金秋医院门诊就诊及住院的患者,年龄≥65岁,确诊CSVD的患者319名。采用脑小血管病总负担评分方法对无症状腔隙性梗死、脑白质病变、脑微出血及血管周围间隙扩大等4种CSVD神经影像学特征进行总体评估,记为0～4分。按分值分为轻度组(0分) 145例;中度组(1～2分) 131例和重度组(3～4分) 43例。应用简易智力状态检查量表(MMSE)、蒙特利尔认知评估量表(MoCA)评估认知功能,并进行统计学分析。结果 CSVD重度组年龄与CSVD总负担评分呈正相关(r=0. 841,P=0. 035)。在MMSE评分中,重度组在记忆力子项分值低于轻度组;中、重度组在回忆能力子项分值低于轻度组(P=0. 029、0. 036)。在MoCA评分中,重度组在记忆力、语言能力子项分值低于轻度组(P=0. 031、0. 029);中、重度组在视空间与执行能力、延迟回忆子项分值低于轻度组(P=0. 036、0. 014)。结论 CSVD总负担评分是导致全脑损害的脑小血管病有效的影像学评估手段,CSVD总负担加重与整体认知下降相关,是认知功能障碍的预测因素。多种神经影像学特征合并存在的老年脑小血管病在记忆、延迟回忆、视空间执行能力、语言能力4个认知领域受损更重。     

全血黏度与脑小血管病的相关性研究

目的探讨全血黏度与脑小血管病(SVD)相关性。方法选取正常对照组35例和脑小血管病组35例,根据头颅MRI表现将SVD组分为脑白质病变(WML)组和腔隙性脑梗死(LI)组,比较SVD组、WML组、LI组与正常对照组的全血黏度及其他脑血管危险因素,并对全血黏度进行多因素Logistic回归分析。结果全血黏度的增高与SVD及WML的发生相关(OR=1.518;1.503),当调整其他危险因素后,P0.05;全血黏度的增高与LI的发生相关(OR=1.272),然而调整其他脑血管危险因素后,P0.05。结论全血黏度的增高可能是脑小血管病特别是WML的独立危险因素,其与脑小血管病特别是脑白质病变密切相关。     

脑白质病变合并脑微出血相关危险因素研究

目的探讨脑白质病变(WML)合并脑微出血(CMB)的相关危险因素。方法收集2014年1月~2017年6月黄山市人民神经内科住院患者中符合脑小血管病诊断,且经头颅MRI证实存在WML者94例,其中磁敏感成像(SWI)检测有CMB者59例为CMB组,无CMB者35例为非CMB组。对两组间人口学资料,高血压病史、糖尿病史、卒中史、吸烟史、饮酒史及相关血液指标进行分类、分型后进行统计分析。结果CMB组患者吸烟史、高血压病史的比例及WML严重程度评分、血UA明显高于非CMB组(均P0.05)。单因素回归分析示血UA高、吸烟史、高血压病史及WML严重程度评分高与WML患者合并CMB密切相关(均P0.05);进一步多因素回归分析示血UA高(OR=1.007,95%CI:1.002~1.012,P=0.009)、WML严重程度评分高(OR=1.584,95%CI:1.085~2.313,P=0.017)是WML患者合并CMB的独立危险因素。结论高血UA、重度WML为WML患者合并CMB的独立危险因素。     

口腔菌群在脑小血管病发病机制中的研究进展

正脑小血管病(cerebral small vessel disease,CSVD)在老年患者认知障碍和痴呆的病理生理机制中具有重要的意义[1]。其主要影像学表现为脑白质高信号(white matter hyperintensity,WMH)、腔隙性梗死(lacunar infarction,LI)、脑微出血(cerebral microbleeds,CMB)、扩大的血管周围间隙(perivascular spaces,PVS)和脑萎缩。虽然其临床表现通常是隐匿的,但以上脑部病变的存在常与肢体功能障碍、认知障碍、步态异常、膀胱功能障碍和死亡的风险相关[2]。高血压、糖尿病等传统危险因素在CSVD发病中起重要作用,但其确切的发病机制尚不清楚。目前研究表明,血脑屏障(Blood-brain barrier BBB)和内皮功能障碍与CSVD有关[3]。     

肠管菌群血液代谢物与脑小血管病相关性研究

<正>脑小血管病(cerebral small vessel disease,CSVD)是一种常见的隐袭性脑血管病,由于多起病隐匿,临床存在静寂现象,容易被患者甚至临床医师忽视。主要影像学表现为腔隙性梗死(lacunar infarction,LI)、脑白质高信号(white matter hyperintensity,WMH)、血管周围间隙扩大(enlarged perivascular spaces,EPVS)、脑微出血(cerebral microbleed,CMB)和脑萎缩。随着CSVD负担逐渐加重,患者可出现认知障碍、运动障碍、情感障碍和二便障碍等症状^[1]。     

血浆同型半胱氨酸与不同类型脑小血管病相关性分析

目的：分析血同型半胱氨酸（Hcy）与不同类型脑小血管病的相关性。方法纳入脑小血管病患者123例（病例组）,其中单纯脑白质疏松症（LA）39例,腔隙性梗死（LI）35例,脑微出血（CMB）16例,脑白质疏松并腔隙性梗死和（或）脑微出血33例,40例健康者为对照组。对2组患者均进行Hcy检测。结果LA、LI、CMB及脑白质疏松并腔隙性梗死和（或）脑微出血组血浆同型半胱氨酸均高于对照组（P＜0.05）,脑白质疏松并腔隙性梗死和（或）脑微出血组血浆同型半胱氨酸明显高于其他3组脑小血管病组（P＜0.05）,LA、LI及CMB血浆同型半胱氨酸无明显差异。结论Hcy与脑小血管病（SVB）的病情严重程度具有密切关系。     

脑小血管病诊断及治疗现状

正脑小血管病(cerebral small vessel disease,CSVD)是指脑内直径200μm的小动脉、微动脉、毛细血管、微静脉、小静脉发生的各种原因的病变引起的一系列病理学、影像学、临床症状、体征等表现的综合征。病人的脑小血管发生玻璃样变、纤维素样坏死、小动脉硬化等病理改变,脑组织则可发生脑微出血(cerebral microbleeds,CMB)、脑白质疏松(whitematter lesions,WML)、血管周围间隙增宽(enlarge     

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.     

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.     

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.     

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.     

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.     

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.