创伤性脑损伤后认知障碍研究现状

创伤性脑损伤(traumatic brain injury,TBI)具有较高的发生率,尤其是在当代社会工业和经济高度发达的社会中.TBI后遗症多,残、死率高,不仅给患者本人及其家庭带来了巨大痛苦,也对社会造成了沉重的负担.TBI的严重后果包括:①运动功能缺陷;②知觉障碍;③认知缺陷;④语言障碍;⑤人格改变等.认知障碍为TBI最常见、最持久的后遗症状之一.本文就TBI后认知障碍的研究现状进行简要概述.     

科学基金对颅脑创伤研究的促进作用

颅脑创伤,又称创伤性脑损伤(traumatic brain injury,TBI),是由外伤引起的脑组织损害.在世界范围内,TBI已成为继心脏病、恶性肿瘤、脑血管意外之后的第4位死因[1].美国TBI发生率约为538/10万,其中,约有32％是因为坠落造成的,19％是交通意外,18％归咎于斗殴或运动伤害[2].值得注意的是,交通意外是造成青壮年重型TBI的首要原因,而绝大部分的跌落伤是发生在5岁以下的儿童或者75岁以上的老年人[3].中国每年大约有100多万人发生TBI,死亡10万余人,20多万人遗留长期昏迷(植物人)、瘫痪、痴呆、语言功能丧失、记忆功能减退等各种神经功能残疾.重型TBI存活的患者脑神经功能残疾发生率高达54％～84％,每年造成的直接和间接经济损失数达百亿元.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

创伤性脑损伤后认知障碍发生机制的研究进展

创伤性脑损伤(traumatic brain injury,TBI)也称为脑外伤,其发生率高、死残率高、后遗症多,给患者及家庭造成极大的痛苦和经济负担也给社会带来沉重的负担.TBI的严重后果包括:运动功能缺陷、知觉障碍、认知缺陷、语言障碍、外伤性癫痫、人格改变等,其中认知障碍为最持久和最严重的症状之一,通常表现在注意力和记忆力两方面.研究表明空间记忆缺失发生于各种程度的TBI之后,而有关TBI之后认知障碍的确切机制至今仍不十分清楚.     

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.     

Epilepsy and anomalies of neuronal migration: MRI and clinical aspects

Neuronal migration disorders are the result of disturbed brain development. In such disorders, neurons are abnormally located. In diagnosing these conditions, magnetic resonance imaging is superior to any other imaging technique. This enables us to improve our knowledge of the clinical correlates of neuronal migration. With reference to migrational disorder, a retrospective study of all 303 patients with epileptic seizures referred for magnetic resonance imaging during a 3-year period was performed, 13 patients (aged 12-41, mean age 27) were identified. They represent 4.3% of the entire study group. Of the patients with known epilepsy, 6.7% and of the mentally retarded, 13.7% had migrational disorders. Four patients had schizencephaly as the dominant finding, one was classified as hemimegalencephaly, 2 had isolated heterotopias, and 6 had localized pachy- and/or poly-microgyria. The clinical pictures are complex. Ectopias of grey matter are recognised foci of epilepsy, but from an epileptological and a clinical viewpoint little attention has been given to these disorders. The present study shows that malmigration is not rare in epilepsy patients, especially not in the mentally retarded.     

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.     

Classification of methods in transcranial Electrical Stimulation (tES) and evolving strategy from historical approaches to contemporary innovations

Transcranial Electrical Stimulation (tES) encompasses all methods of non-invasive current application to the brain used in research and clinical practice. We present the first comprehensive and technical review, explaining the evolution of tES in both terminology and dosage over the past 100 years of research to present day. Current transcranial Pulsed Current Stimulation (tPCS) approaches such as Cranial Electrotherapy Stimulation (CES) descended from Electrosleep (ES) through Cranial Electro-stimulation Therapy (CET), Transcerebral Electrotherapy (TCET), and NeuroElectric Therapy (NET) while others like Transcutaneous Cranial Electrical Stimulation (TCES) descended from Electroanesthesia (EA) through Limoge, and Interferential Stimulation. Prior to a contemporary resurgence in interest, variations of transcranial Direct Current Stimulation were explored intermittently, including Polarizing current, Galvanic Vestibular Stimulation (GVS), and Transcranial Micropolarization. The development of these approaches alongside Electroconvulsive Therapy (ECT) and pharmacological developments are considered. Both the roots and unique features of contemporary approaches such as transcranial Alternating Current Stimulation (tACS) and transcranial Random Noise Stimulation (tRNS) are discussed. Trends and incremental developments in electrode montage and waveform spanning decades are presented leading to the present day. Commercial devices, seminal conferences, and regulatory decisions are noted. We conclude with six rules on how increasing medical and technological sophistication may now be leveraged for broader success and adoption of tES.     

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.     

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.     

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.