帕金森病患者认知功能障碍与抑郁临床分析

目的探讨帕金森病(PD)患者的认知功能障碍及抑郁的特点及关系。方法对50例PD患者和42例对照组进行认知功能及抑郁评定和分析。结果 PD组同对照组相比,简易精神状况检查(MiniMental State Examination,MMSE)及蒙特利尔认知评估(Montreal Cognitive Assessment,MOCA)量表各因子分,除语言因子分外均有显著性差异(P<0.05),汉密尔顿抑郁量表(Hamilton depression scale,HAMD)均分和抑郁自评量表(Self-rating Depression Scale,SDS)均分均有显著性差异(P<0.05),抑郁严重程度与认知功能损害成正相关(r=0.438)。结论 PD患者存在认知功能障碍与抑郁,抑郁可能是导致认知功能下降的重要因素。     

脑深部电刺激治疗对帕金森病患者认知功能、抑郁和焦虑的影响

目的探讨双侧丘脑底核脑深部电刺激治疗(STN-DBS)对帕金森病(PD)患者认知功能和抑郁、焦虑状态的影响。方法连续收集16例拟行双侧STN-DBS的PD患者为实验组,在术前1周、术后1月和术后3月行认知功能、抑郁和焦虑状态评估。同期在门诊收集16例优化药物治疗的PD患者为对照组,在相同时间点行同样的神经心理量表评估。结果实验组患者的Mo CA评分与术前(20.69±4.33)相比,在术后1月(19.81±4.34)及术后3月(19.44±5.35)均有下降趋势,但差异无统计学意义(P0.05)。实验组患者的抑郁症状与术前(23.56±14.60)相比,在术后1月(11.94±6.16)及术后3月(7.38±5.18)有明显改善(P0.05)。实验组患者的焦虑症状与术前(22.13±6.11)相比,在术后1月(15.13±5.62)及术后3月(8.00±6.76)有明显改善(P0.05)。抑郁焦虑的改善在任何时期均与UPDRS-Ⅲ无相关性(P0.05)。结论双侧STN-DBS治疗在术后3月时并不影响PD患者的总体认知功能,但各个认知域的改变需要更为详细的神经心理量表评估;双侧STN-DBS治疗在短期内可以显著改善PD患者的抑郁和焦虑症状,且抑郁和焦虑症状的改善与STN-DBS治疗后运动症状的改善无关。     

帕金森病患者血小板5-羟色胺水平的改变及其与抑郁、认知功能障碍的关系

目的探讨帕金森病(PD)患者血小板5-羟色胺(5-HT)水平的改变及其与抑郁、认知功能障碍的关系。方法采用高效液相色谱法检测54例PD患者和54名健康中老年人(正常对照组)的血小板5-HT水平。采用汉密尔顿抑郁(HAMD)量表和简易精神状态检查(MMSE)量表对PD患者进行评分,并对血小板5-HT水平与HAMD和MMSE量表评分进行相关性分析。结果 PD患者血小板5-HT水平比正常对照组显著降低(P<0.05),并且PD伴抑郁、认知功能障碍患者的血小板5-HT水平分别显著低于PD无抑郁及无认知功能障碍患者(均P<0.05)。PD患者血小板5-HT水平与HAMD量表评分呈负相关(r=-0.3310,P<0.05),与MMSE量表评分呈正相关(r=0.5415,P<0.05);PD伴抑郁患者的MMSE量表评分显著低于无抑郁患者(P<0.05)。结论 PD患者的血小板5-HT水平明显降低,并且PD伴抑郁和认知功能障碍患者的血小板5-HT水平降低更明显。     

帕金森病患者轻度认知损害的临床调查

目的 研究帕金森病(Parkinson's disease,PD)伴有轻度认知功能缺损(mild cognitiveimpairment,MCI,即PD-MCI)患者患病率及其神经心理学特征.方法 设立PD患者组(n=103)及健康对照组(n=32)进行比较.心理学测验工具由MMSE、痴呆评定量表及其他神经心理学测试组成,汉密尔顿抑郁量表用以评定患者的抑郁程度.结果 (1)21例(20.4%)PD患者被诊断为痴呆,37例(35.9%)患者认知功能完整,45例(43.7%)患者有MCI;(2)与认知正常的PD患者相比,PD-MCI患者年龄更大,PD起病更晚,且运动损害更为严重;(3)PD-MCI的患病率和神经心理学特征与PD症状主要累及何侧及分型有一定关系:左侧组比右侧组患者出现MCI的概率要高(74.2%和42.2%,χ2=7.589,P<0.05);震颤为主型患者与混合型患者相比,Stroop测词试验(SWT)的耗时(s)显著减少(80.8±39.9和94.4±30.0,t=3.332,P<0.01).结论在PD患者中,筛查出PD-MCI患者有着重要的临床意义,有助于临床医生针对性地处理不同PD患者,并易化对其预后的判断.     

帕金森病患者血清维生素D水平与不同认知域的临床观察

目的观察帕金森病(PD)患者血清维生素D水平和不同认知域的情况,评估血清维生素D水平与PD患者不同认知域的相关性。方法选择77例PD患者及同期34名健康对照者,检测空腹血清维生素D水平,采用认知功能相关量表对PD患者、健康对照者进行认知功能评分,同时进行PD患者运动功能和抑郁程度评分。结果 PD患者的血清维生素D水平较健康对照组的明显降低(t=-3.154,P=0.002)。PD痴呆组和非痴呆组的MMSE评分及蒙特利尔认知评估量表评分较健康对照组的明显降低(均P0.05)。PD痴呆组、PD非痴呆组与健康对照组相比,在多项认知功能领域评分有明显差异(均P0.05)。PD患者血清维生素D水平与病程和Hoehn-Yahr分期有显著负相关性(r_1=-0.372,P_1=0.002;r_2=-0.292,P_2=0.010)。PD非痴呆组的血清维生素D水平分别与听觉词语学习测试中即刻回忆、短延迟记忆、长延迟记忆(P_1=0.005;P_2=0.007;P_3=0.014)具有显著正相关性。结论 PD患者血清维生素D水平较正常人群明显降低,血清维生素D水平与PD患者的疾病病程、严重程度呈显著负相关,与PD非痴呆患者的记忆功能呈显著正相关,血清维生素D水平对于非痴呆PD患者的记忆功能具有一定的影响。     

脑卒中后抑郁与认知功能的相关性研究

目的探讨脑卒中后抑郁与认知功能相关性,为脑卒中后抑郁认知功能提供依据。方法采用前瞻性研究方法,将200例脑卒中患者分为抑郁组(观察组)和非抑郁组(对照组),评估2组的生活质量及认知功能。结果观察组BI和AS评分分别为(60.52±8.09)和(16.26±2.83),对照组为(54.36±7.11)和19.58±3.49),差别有统计学意义(P0.05);观察组定向力、视空间与执行功能、延迟回忆和注意力分别为(4.30±1.02)、(3.19±0.97)、(3.41±0.86)和(4.12±1.01),均低于对照组(4.86±1.24)、(3.88±1.05)、(4.08±1.17)和(4.82±1.33),差别有统计学意义(P0.05);观察组MoCA和ADL评分分别为(20.98±8.46)和(51.36±6.17),对照组为(25.01±9.51)和(57.82±6.45),差别有统计学意义(P0.05)。结论脑卒中后抑郁患者生活质量与认知功能均较低,改善脑卒中患者认知功能,对于维持卒中患者的日常生活能力和生活质量有重要意义。     

帕金森病患者外周血单核细胞趋化蛋白-1及巨噬细胞炎性蛋白-1α水平与非运动症状的相关性研究

目的检测帕金森病(PD)患者血清单核细胞趋化蛋白-1(MCP-1)、巨噬细胞炎性蛋白-1α(MIP-1α)水平,并探讨其与PD、尤其与非运动症状(non-motor symptoms,NMS)的相关性。方法采用ELISA法对67例PD组患者及年龄、性别匹配的34例正常对照组血清MCP-1、MIP-1α水平进行检测。采用UPDRSⅢ评分和Hoehn-Yahr分级对PD患者运动功能进行评估,将其分为早期、中晚期;用PD非运动症状评定量表(NMSQuest)对NMS损害程度进行总体评估;用汉密尔顿抑郁量表(HAMD)、汉密尔顿焦虑量表(HAMA)、简易精神状态评价量表(MMSE)对患者抑郁、焦虑、认知功能评估,并用Pearson直线相关分析检验MCP-1、MIP-1α浓度与各量表评分之间的相关性。结果 PD患者血清MCP-1、MIP-1α水平明显高于健康对照组(P0.01);血清MCP-1、MIP-1α水平与抑郁、焦虑、认知功能呈显著正相关,特别是发现PD早期患者血清MCP-1、MIP-1α水平与HAMD评分呈显著正相关,PD中晚期患者血清MCP-1、MIP-1α水平与MMSE评分呈负相关;中晚期PD患者血清MCP-1、MIP-1α水平显著高于PD早期,PD合并抑郁、认知功能障碍组血清MCP-1、MIP-1α水平显著高于PD未合并抑郁、认知功能正常组(P均0.01)。结论血清MCP-1、MIP-1α可能参与PD的发病过程,在PD早期与抑郁显著正相关,在PD晚期与认知功能障碍显著正相关。PD患者血清MCP-1、MIP-1α水平随着运动症状、非运动症状(如抑郁、认知功能)的加重而升高。     

无症状脑梗死患者认知功能障碍及抑郁与事件相关电位变化的关系

目的探讨无症状脑梗死(SBI)患者认知功能障碍及抑郁与事件相关电位(ERP)变化的关系。方法对68例SBI患者采用汉密尔顿抑郁(HAMD)量表、简易精神状态检查(MMSE)量表及ERP检查,并与55例非脑梗死患者(对照组)进行比较。结果SBI组中,31例(45.6%)HAMD≥17分(抑郁亚组),37例(54.4%)HAMD<17分(非抑郁亚组)。SBI组MMSE评分(17.1±1.8)较对照组(25.2±1.6)显著降低,认知功能障碍发生率(52.9%vs 12.7%)显著增高(均P<0.05);与对照组相比,SBI组P3潜伏期显著延长,波幅显著降低(均P<0.05)。SBI组中,抑郁亚组MMSE评分(14.9±1.2)较非抑郁亚组(21.6±2.6)显著降低,认知功能障碍发生率(93.6%vs 21.6%)显著增高,P3潜伏期明显延长和波幅明显降低(均P<0.05)。SBI抑郁亚组MMSE评分与P3潜伏期负相关,与波幅正相关(r=-0.537,r=0.529;均P<0.05)。结论SBI患者存在认知功能障碍,伴抑郁症状者认知功能障碍更显著。ERP检查可早期发现SBI患者的认知功能障碍及抑郁。     

Parkinson病患者认知功能障碍与失匹配负波相关性研究

目的：探讨失匹配负波（MMN）与额叶认知功能测试在评价Parkinson病（PD）患者认知功能中的作用及其临床价值。方法：对28例早期非痴呆非抑郁PD患者和31例年龄、教育年限相匹配的正常对照组分别进行额叶认知功能测试和MMN测定。结果：与正常对照组相比，非痴呆非抑郁PD患者额叶认知测试评分较差，MMN潜伏期延长（P〈0．001）；波幅虽呈下降趋势，但无统计学意义；MMN潜伏期延长与额叶认知功能障碍程度呈正相关（P〈0．01～0．05）。结论：MMN能较客观地反映非痴呆非抑郁PD患者早期额叶认知功能障碍。     

帕金森病伴认知障碍患者血尿酸变化及相关因素分析

目的探讨帕金森病患者认知功能和血尿酸水平的关系并对认知功能相关因素进行分析。方法入选PD患者78例和年龄、性别相匹配的40例健康对照组,记录PD患者的性别、年龄、病程、受教育年限、HoehnYahr(H-Y)分级,采用蒙特利尔认知评估量表(Mo CA)对所有研究对象认知功能进行评估,对血尿酸、尿微量白蛋白水平进行检测。结果 PD组血尿酸水平明显低于健康对照组[(258.16±57.58)μmol/L比(330.23±52.92)μmol/L,P0.01];早期PD组与中晚期PD组血尿酸水平无明显差异(P0.05);但合并轻度认知功能障碍(MCI)的PD组血尿酸水平低于无MCI的PD组[(235.16±68.36)μmol/L比(272.58±59.69)μmol/L,P0.01];各亚组间及各亚组与对照组比较尿微量白蛋白水平无明显差异(P0.05);PD患者Mo CA评分与受教育年限(β=0.552,P0.01)、血清尿酸水平(β=0.483,P0.01)呈正相关,与病程(β=-0.469,P0.05)、H-Y分级(β=-0.324,P0.05)呈负相关。结论尿酸水平的改变可能参与了PD患者的发病机制;血尿酸水平下降可能是PD合并认知障碍的一个重要危险因素,对血尿酸水平进行适当干预可能有助于提高帕金森病患者的生活质量。     

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.     

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.     

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.