伴颈动脉粥样硬化的急性脑梗死患者胰岛素抵抗与TNF-α关系的临床研究

目的探讨肿瘤坏死因子α(TNF-α)与胰岛素抵抗(IR)在伴颈动脉粥样硬化(CAS)的急性脑梗死中的作用机制及二者之间的关系。方法比较44例伴CAS的急性脑梗死患者与80例健康对照组中空腹血糖(FPG)、空腹血清胰岛素(FINS)、胰岛素敏感指数(ISI)、胰岛素抵抗指数(HOMA-IR)、TNF-α、体重指数(BMI)等6个因素之间有无差异,并了解IR与TNF-α的相关性。结果伴CAS的急性脑梗死组与对照组相比,FPG、FINS、HOMA-IR、TNF-α明显高于对照组,ISI明显低于对照组(P<0.01或P<0.05);脑梗死组中,ISI与TNF-α呈显著负相关(r=-0.494,P<0.01)。结论在伴有CAS的急性脑梗死中同时存在IR及TNF-α升高,IR程度与TNF-α呈正相关。     

利培酮治疗的分裂症患者催乳素与胰岛素敏感性相关性的初步研究

目的初步探讨利培酮治疗的分裂症患者催乳素水平与胰岛素敏感性的相关性。方法对符合入组标准的51例服用利培酮治疗的住院分裂症患者记录年龄、利培酮的使用剂量、分裂症病期等一般情况,测量身高、体重,并检测空腹血糖、血清催乳素及胰岛素(FINS)。计算稳态模型的胰岛素抵抗指数(HOMA-IR)和QUICKI胰岛素敏感性指数。依据体重指数(BMI)将患者分为正常体重组(BMI:18.5～23.9)和超重组(BMI≥24kg/m2),使用Pearson相关分析分析血清催乳素与胰岛素敏感性指标的相关性。结果催乳素与FINS、HOMA-IR、QUICKI胰岛素敏感性指数(r=0.149,P>0.05;r=0.134,P>0.05;r=-0.103,P>0.05)均无统计意义的相关性。正常体重组与超重组的催乳素水平无统计学差异(t=0.597,P>0.05)。超重组FINS、HOMA-IR高于正常体重组(t=2.679,P<0.05;t=2.753,P<0.05),超重组QUICKI胰岛素敏感性指数低于正常体重组(t=3.697,P<0.01)。结论服用利培酮治疗的分裂症患者催乳素水平与胰岛素抵抗无统计意义的相关性。     

合并OSAHS的老年急性脑梗死患者同型半胱氨酸和胰岛素抵抗临床分析

目的研究合并阻塞性睡眠呼吸暂停综合征(OSAHS)的老年急性脑梗死(ACI)患者血清同型半胱氨酸(Hcy)及稳态模型胰岛素抵抗指数(HOMA-IR)水平,分析老年ACI患者OSAHS、Hcy和HOMA-IR相互关系。方法根据年龄和睡眠呼吸监测数据,将患者分为老年ACI+OSAHS组(n=21)、老年ACI组(n=30)、中年ACI+OSAHS组(n=28)和中年ACI组(n=34),检测并比较各组血清Hcy、胰岛素抵抗指数(HOMA-IR)等各指标。结果老年ACI+OSAHS组较其余3组的Hcy和HOMA-IR均升高,差异有统计学意义(P0.05);中年ACI+OSAHS组较中年ACI组Hcy和HOMA-IR增高,差异有统计学意义(P0.05)。Hcy与年龄、AHI、平均腰围、BMI、HOMAIR均呈正相关;多元线性回归分析显示AHI与年龄、Hcy、HOMA-IR、BMI呈正相关。结论随年龄的增加,合并OSAHS的急性脑梗死患者Hcy和HOMA-IR水平随之升高;OSAHS可能通过升高Hcy及增加胰岛素抵抗导致ACI。     

脑白质疏松与胰岛素抵抗和单核细胞趋化蛋白-1的关系

目的探讨脑白质疏松患者胰岛素抵抗(IR)与血浆单核细胞趋化蛋白-1(MCP-1)水平的关系。方法选择48例脑白质疏松患者,以30例健康者作为对照组。采用放射免疫法测定两组的空腹血胰岛素(FINS)水平,同时检测空腹血糖(FBG)、血脂,以稳态模型评估法(HOMA)评价胰岛素抵抗(HOMA-IR)。采用ELISA法测定血清MCP-1水平。结果脑白质疏松组的MCP-1水平高于健康对照组(P<0.01);脑白质疏松组FINS、HOMA-IR均高于健康对照组(P<0.01)。相关性分析显示脑白质疏松患者血清MCP-1水平与FPG、TC、LDL-C、血清胰岛素、HOMA-IR呈明显正相关(P<0.01)。结论脑白质疏松患者存在胰岛素抵抗,MCP-1与胰岛素抵抗密切相关。     

OSAS患者血清同型半胱氨酸水平与胰岛素抵抗及其相互关系

目的通过观察OSAS患者血清同型半胱氨酸（Hcy）及胰岛素抵抗水平,分析两者之间的关系,进一步探讨OSAS患者高同型半胱氨酸血症及脑梗死发生的可能机制。方法按照便携式睡眠呼吸监测仪的监测数据,将入选者分为OSAS组（n=42）与对照组（n=40）,检测入选者空腹血清Hcy、血糖、血清胰岛素水平,计算出胰岛素抵抗指数（HOMA-IR）;比较2组血清Hcy、HOMA-IR水平,探讨血清Hcy与HO-MA-IR的关系。结果 OSAS组的血清Hcy、HOMA-IR水平较对照组显著增高（P〈0.05）,血清Hcy与HOMA-IR呈正相关（r=0.815,P〈0.01）,经偏相关分析校正体重指数及年龄的影响后它们之间仍呈正相关（r＇=0.715,P〈0.01）。结论 OSAS可能通过胰岛素抵抗的增强而影响Hcy的代谢,引起高同型半胱氨酸血症,进而导致脑梗死的发生。     

胰岛素抵抗对2型糖尿病患者周围神经病变的影响

目的探讨及分析胰岛素抵抗对2型糖尿病患者周围神经病变的影响。方法选取2型糖尿病患者161例为研究对象,按照是否合并周围神经病变将患者分为糖尿病周围神经病变组(DPN组,n=102)和非糖尿病周围神经病变组(NDPN组,n=59);比较2组一般资料、餐后胰岛素敏感性(Matsuda指数)、空腹胰岛素抵抗(HOMA-IR)、空腹及糖耐量实验(OGTT)后各时间点的血糖、胰岛素素及C-肽水平之间的差异。结果 DPN组年龄、糖尿病病程、HbA1c、LDL-C水平均高于NDPN组,差异有统计学意义(P0.05),Matsuda指数、HOMA-IR、空腹血糖及胰岛素水平[OGTT(0 min)]均高于NDPN组(P0.05),OGTT(120min)胰岛素水平显著低于NDPN组(P0.05);Logistic回归分析提示:年龄、空腹血糖(FBG)、胰岛素(FIRI)水平、HOMA-IR、Matsuda指数与患者周围神经病变的发生呈正相关(P0.05),而OGTT(120min)胰岛素水平与其呈负相关(P0.05)。结论 2型糖尿病患者空腹胰岛素抵抗与周围神经病变的发生密切相关,而患者餐后胰岛素抵抗则可能对周围神经病变的发生起到抑制作用。     

脑梗死患者胰岛素抵抗与血管内皮功能损伤机制研究

目的 通过检测脑梗死患者胰岛素抵抗水平以及血管内皮功能损伤程度,以探讨胰岛素抵抗与血管内皮损伤的相关性.方法 试验分组:脑梗死合并高血压患者30例,脑梗死合并高血压及糖尿病患者25例,无脑梗死、高血压、糖尿病的患者20例作为对照组.以胰岛素稳态(HOMA-IR)方法检测患者胰岛素抵抗水平,以ELISA方法检测患者血管内皮功能(ADMA、VE-Ca)的损伤程度.结果 (1)脑梗死组患者的HOM A-IR高于对照组(P＜0.01),脑梗死合并高血压及糖尿病组患者的HOMA-IR高于脑梗死合并高血 压组患者(P＜0.01).(2)脑梗死组患者的内皮功能损伤较对照组严重,血清ADMA、VE-Ca浓度高于对照组(P＜0.01),脑梗死合并高血压及糖尿病组患者血管内皮功能损伤程度较脑梗死合并高血压组严重,血清ADMA、VE-Ca浓度增高明显(P＜0.01).(3)胰岛素抵抗与血管内皮功能损伤存存明显的相关性,ADMA随着HOMA-IR的升高而升高,R=0.901(P＜0.01),VE-Ca亦随着HOMA-IR的升高而升高,R=0.932(P＜0.01).结论 脑梗死患者存在血管内皮功能损伤,危险因素越多,血管内皮功能损伤越严重,其机制可能通过胰岛素抵抗引起.     

胰岛素抵抗、血脂异常与急性脑梗死关系的初步研究

目的探讨胰岛素抵抗、血脂异常与急性脑梗死之间的关系.方法对45例急性脑梗死患者作空腹血糖(FPG)、血清胰岛素(FINS)及血脂测定,并与25例原发性高血压(EH)患者及25例健康体检者比较.采用李光伟提出的方法计算胰岛素敏感性指数(ISI)为空腹血清胰岛素与空腹血糖乘积的倒数,即1/(FINS×FPG),取其自然对数.结果急性脑梗死患者FINS明显高于两对照组(P＜0.01);胰岛素敏感性指数明显低于两健康对照组(P＜0.01);TG、CHOL、apoB明显高于健康对照组(P＜0.01),HDL明显低于对照组(P＜0.01).FPG、LDL及apoA1三组间无明显差异.结论急性脑梗死存在胰岛素抵抗,胰岛素抵抗和血脂异常可能在脑梗死的发生中起重要作用.胰岛素抵抗在脑梗死中的重要作用有待于进一步深入研究.     

胰岛素抵抗与急性脑梗死严重程度关系研究

目的 探讨胰岛素抵抗与急性脑梗死严重程度的关系.方法 选取急性脑梗死患者75 例,按神经功能缺损评分标准将急性脑梗死组分为神经功能缺损轻型组和中重型组,对照组为同期门诊健康体检者55例.各组分别检测空腹血糖、空腹血清胰岛素、纤维蛋白原、总胆固醇、甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A蛋白、载脂蛋白B蛋白、尿酸,计算体重指数、胰岛素敏感指数、胰岛素抵抗指数,进行统计学分析.结果 急性脑梗死组FPG、FINS、HOMA-IR、FIB显著高于对照组,急性脑梗死神经功能缺损中重型组中FPG、FINS、HOMA-IR显著高于轻型组,差异均有统计学意义.结论 急性脑梗死患者存在IR,神经功能缺损中重型组较轻型组存在更严重的IR,并且IR 程度与神经功能缺损的严重程度有关.     

睡眠时长对抑郁症患者胰岛素抵抗水平的影响

目的研究抑郁症患者不同睡眠时长对其胰岛素抵抗水平的影响,为抑郁症患者糖尿病的病因学机制研究提供参考。方法于2012年10月-2015年12月在天津市精神卫生中心精神科门诊及住院患者中抽取86例重度抑郁症患者,均符合《精神障碍诊断与统计手册(第4版)》(DSM-IV)诊断标准。检测患者空腹血糖(FBG)、空腹血清甘油三酯(FTG)水平;采用FBG和FTG水平计算所得简易胰岛素抵抗指数(Ty G)评估受试者胰岛素抵抗水平;采用匹兹堡睡眠指数量表(PSQI)评估患者睡眠情况,根据评估结果计算患者近1个月的日均睡眠时长,按日均睡眠时间长短将患者分为极短时组(4h)、短时组(4~6h)、参照组(6~8h)和长时组(≥8h),比较四组胰岛素抵抗水平;采用多重线性回归分析胰岛素抵抗水平的影响因素。结果与参照组比较,极短时组与短时组FBG和FTG水平更高,但各组之间差异无统计学意义(P均0.05);极短时组与短时组的平均简易胰岛素抵抗指数高于参照组(P0.05);多重线性回归分析结果显示,胰岛素抵抗指数与年龄(β=0.005,P0.05)、BMI(β=0.012,P0.05)正向关联,与睡眠时长(β=-0.014,P0.05)负向关联。结论短时睡眠可能是抑郁症患者发生胰岛素抵抗进而诱发糖尿病的危险因素之一。     

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.