阿尔茨海默病相关嗅觉障碍研究进展

阿尔茨海默病(Alzheimer disease,AD)的典型表现为进行性记忆力下降和逐渐加重的认知功能障碍,AD患者出现典型表现时多处于疾病中晚期,已经错过了治疗的最佳时期。多项研究表明AD患者早期即可出现嗅觉功能障碍,且出现时间早于情景记忆下降等典型表现。本文对AD患者相关嗅觉功能障碍的病理、临床表现、嗅觉功能障碍检测方法及其应用等方面的进展进行综述。     

原发性震颤患者的非运动症状

目的 研究原发性震颤(essential tremor,ET)患者嗅觉障碍等非运动症状的发生情况.方法 对62例ET患者应用震颤评分量表(Falm-Tolosa-Matin Tremor Rating Scale,TRS)、帕金森病非运动症状30问卷量表(Parkinson's disease non-motor symptoms questionnaire,NMS Quest)和MMSE进行评分,T&T标准嗅觉测试液检测嗅觉功能,并与60名健康体检者进行对照.结果 ET患者的嗅觉障碍发生率为51.6%(32/62),明显高于健康对照组(30.0%,18/60,x~2=12.371,P<0.05);平均每例ET患者出现5项左右不同的非运动症状,以对近期发生的事情记忆有困难或忘记做一些事情、嗅觉障碍、令人紧张或害怕的梦或生动梦境的发生率较高.嗅觉障碍等非运动症状的发生与ET患者的病程、病情严重程度、治疗与否没有明显的相关性.结论 除姿势性震颤或动作性震颤外,ET患者还会出现嗅觉障碍等非运动症状,需要全面认识和及时干预.     

嗅觉障碍与帕金森病关系的研究进展

帕金森病(Parkinson's disease,PD)是一种常见的神经系统退行性疾病,在我国60岁以上的老年人中患病率超过1000/10万,且随年龄的增长而增高,严重影响了老年人的生活质量.自认识本病以来,一直将运动迟缓、肌强直、静止性震颤和姿势平衡障碍等运动症状作为其主要表现并成为诊断依据.近年来,随着对PD非运动症状的关注,越来越多的研究表明PD患者存在嗅觉功能的减退,甚至在疾病的早期就出现了嗅觉功能的改变.本文就嗅觉障碍与帕金森病关系的研究进展作一综述.     

轻度认知功能障碍与阿尔茨海默病患者感觉障碍 及其电生理改变研究进展

阿尔茨海默病（AD）是最常见的中枢神经退行性疾病之一，常隐匿起病，目前尚缺乏有效 的治疗手段。轻度认知障碍（MCI）是介于正常衰老与痴呆之间的一种认知功能损害状态，部分MCI可 发展成为AD。AD 的核心临床症状主要为记忆障碍、认知功能障碍、人格和行为改变。多项研究表明 AD 可能伴随有感觉障碍，如嗅觉、视觉、听觉等，其中嗅觉障碍可能是MCI 或AD 早期的临床症状之一， 并且在MCI 及AD 患者中可出现感觉相关电生理改变。现就MCI 及AD 患者感觉障碍及其电生理研究进 行综述。     

早期与中晚期帕金森病非运动症状的比较以及对生活质量的影响

目的比较早期与中晚期帕金森病(PD)非运动症状(NMS)及其对生活质量的影响。方法采用非运动并发症30题问卷(PDNMS)以及39项帕金森病生活调查表(PDQ39)评价82例早期PD患者(早期组)及69例中晚期PD患者(中晚期组)的NMS及健康相关生活质量。结果早期组及中晚期组患者的便秘、兴趣缺乏、幻觉、错觉、嗅觉减退、吞咽困难、排便不尽感、夜尿、跌倒、日间思睡、失眠及多汗发生率差异有统计学意义(P 0. 05～0. 01)。早期及中晚期PD患者PDNMS总分与PDQ39总分及各维度评分呈正相关(P 0. 05～0. 01)。早期PD患者PDNMS的注意力下降、兴趣缺乏以及抑郁与PDQ39总分具有相关性(r=0. 420,r=0. 366,r=0. 364;均P 0. 01);中晚期PD患者PDNMS的兴趣缺乏、日间思睡及流涎与PDQ39总分具有相关性(r=0. 396,r=0. 380,r=0. 371;均P 0. 01)。结论注意力下降、兴趣缺乏及抑郁对早期PD患者生活质量影响较大,而兴趣缺乏、日间思睡及流涎对中晚期PD患者生活质量影响较大。     

人类免疫缺陷病毒相关脊髓病研究进展

随着高效抗逆转录病毒疗法的广泛应用,人类免疫缺陷病毒(HIV)感染致局灶性或弥漫性神经系统损害发生率降低,显著改善HIV感染患者生活质量,但仍有70%患者出现中枢或周围神经系统症状。这些并发症常出现在疾病晚期或重度免疫功能损害时,亦可出现于疾病早期。HIV相关脊髓病是人类免疫缺陷综合征较常见的并发症,典型病理改变为空泡样变性。多数患者仅表现为非特异性括约肌功能障碍和性功能障碍,少部分患者甚至无临床症状,当出现明显运动和感觉症状时,常合并周围神经病变,故临床易忽视。本文拟就HIV相关脊髓病的发病机制、临床表现、病理学特点、诊断与治疗研究进展进行简要概述。     

艾滋病毒感染者的嗅觉识别缺损

许多中枢神经系统疾病,如阿尔采默氏病、Down氏综合征、帕金森氏病等,早期都出现嗅觉识别缺损。在大部分艾滋病毒感染者中,人类免疫缺陷病毒(HIV)也影响了中枢神经系统(CNS)。为了证明嗅觉识别缺损可以表明其中枢神经系统有病变,本文作者对3个病人组和一个对照组进行了嗅觉识别检测。方法:病人按免疫缺陷逐步进展的连续谱分组:一组是无症状、HIV血清反应阳性,HIV抗体检测阳性、全身情况好、没有接受任何治疗的病人,为无症状组;一组是     

嗅棒气味识别能力测试在中国帕金森病患者中的运用:一项配对病例对照研究

作为帕金森病(Parkinson's disease,PD)最为常见的非运动症状之一,嗅觉减退在PD的早期诊断及鉴别诊断中具有重要作用.西方研究数据显示,作为疾病早期预警指标之一,嗅觉减退可见于90％的PD患者.通过对嗅觉的分析有助于特发性震颤、进行性核上性麻痹、皮质基底节变性及Parkin突变PD与散发性PD的鉴别诊断.     

帕金森病非运动症状研究现状

帕金森病(Parkinson’s disease,PD)是一种中枢神经系统退行性病变,临床上通常以静止性震颤、运动迟缓、齿轮样肌僵直、姿势反射障碍等运动障碍为主要临床表现。一直以来针对帕金森病的治疗方案是以改善患者的运动症状为主要目标,但PD患者通常还会出现感觉障碍(疼痛等)、睡眠障碍(日间过度睡眠等)、自主神经功能异常及精神神经症状(抑郁、躁狂及情感障碍)等,称之为非运动症状(non-motor symptoms,NMS)。有资料显示PD的某些非运动症状与年龄、疾病的严重程度密切相关,对患者生活质量的影响较运动症状更加明显。一些非运动症状,如嗅觉障碍、便秘、抑郁、快速眼动期睡眠行为紊乱(RBD)等,可在疾病早期甚至运动症状出现之前出现,可能对PD的早期诊断有所帮助。非运动症状对患者造成的负担可远远超过运动障碍对患者日常生活和幸福感的影响,深入了解非运动症状,对于PD的预防、治疗及远期预后具有积极意义。本文总结近年来文献并以上述非运动症状的病理、常见临床表现、常用的临床评估及治疗方案为阐述架构,展现近年来PDNMS的研究进展。为了提供一种可以量化的工具,研究者还发明了非运动症状评价量表(NMSS)作为PD非运动症状的临床评价,对严重程度和发作频率进行评估,包含9个方面:心血管、睡眠/疲劳、情绪/认知、感知障碍、注意力/记忆、胃肠道症状、泌尿系统症状、性功能及混合症状,可为临床评价非运动症状的严重程度及治疗提供帮助。     

阿尔茨海默病嗅觉障碍的研究

目的 :研究阿尔茨海默病 (AD)患者嗅觉障碍。方法 :配对的AD患者和正常老年人各 3 0例 ,分别行简易智能状态检查(MMSE)、日常生活活动量表 (ADL)、图片识别试验、气味感知阈值、图片介导的气味识别试验及气味再认记忆试验检查。结果 :AD组的气味感知、气味识别和气味再认记忆功能较正常对照组差 (P <0 0 1) ;相关分析显示 ,AD组患者的嗅觉障碍与MMSE总分密切相关 (P <0 0 5 ) ;结论 :AD患者的嗅觉功能全面受损 ,嗅觉障碍是疾病的早期症状 ,是认知障碍的简单反映     

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.