亚低温脑保护治疗重型颅脑损伤临床病例分析

自80年代以来,通过动物实验研究,其结果证明30～35℃的亚低温能够显降低颅脑损伤后死亡率,能够明显减轻伤后神经功能障碍。近几年来,国外通过临床应用研究结果表明,亚低温脑保护作用能显降低重型颅脑损伤病人的死亡率和病残率。应用亚低温脑保护能降低颅内压,减轻脑水肿,我科自1998年6月～2000年10月共收治110例重型颅脑损伤病人,其中56例应用亚低温治疗,取得了显疗效。     

亚低温治疗重型颅脑损伤病人纤维蛋白原和D-二聚体的变化及其临床意义

目的观察重型颅脑损伤病人在亚低温和常温治疗状态下纤维蛋白原(Fbg)与D-二聚体(D-dimer)差异及其临床意义。方法43例单纯性、重型颅脑损伤病人随机分为亚低温治疗组和常温组,两组性别、年龄、GCS评分无显著差异。伤后5次(6h、12h、24h、48h、72h)检测Fbg和D-dimer,并记录GOS评分。结果①两组Fbg值在伤后6h、12h、24h、48h差异显著,但伤后72h两组差异不显著。两组Fbg值在伤后6h均较高,常温组升高幅度更明显。两组Fbg值在伤后12h下降,亚低温组降低程度较常温组小。②两组D-dimer在伤后6h明显升高,常温组升高更明显;其在伤后6h、12h、24h差异显著,而在伤后48h、72h差异不显著。③亚低温组GOS评分优于常温组,差异显著。结论在颅脑损伤后4h即开始实施亚低温治疗能改善伤后的高凝状态,并减轻继发纤溶亢进。亚低温治疗缓解了凝血功能紊乱,是其能起到脑保护作用和改善治疗效果的机制之一。     

亚低温治疗急性重型颅脑损伤的体会

在重型颅脑损伤的治疗中,亚低温(肛温32～35℃)能显著减轻颅脑损伤后神经功能障碍和脑病理形态损害,保护血脑屏障功能,从而明显降低重型颅脑损伤患者的死亡率,改善预后。我院1996年8月至1999年8月收治80例重型颅脑伤病人,其中40例采用亚低温治疗,取得显著疗效。     

亚低温治疗重型颅脑损伤的经验体会

目的比较亚低温与常温治疗重型颅脑损伤的临床疗效。方法病人被随机分为亚低温治疗组与常温治疗组进行治疗。评价治疗后两组患者神经功能恢复程度和日常生活能力。结果亚低温治疗除对弥漫性轴索损伤者无明显疗效外,对GCS≤5分者,原发性脑干损伤者均有显著的效果。结论亚低温治疗能显著降低重型颅脑损伤患者的颅内压,控制伤后早期的高糖血症。根据颅脑损伤的具体情况来设定亚低温治疗时间。对于GCS≤5分者,伤后6h内行亚低温治疗可明显提高疗效。     

亚低温治疗急性重型颅脑损伤的临床疗效

目的　研究亚低温对急性重型颅脑损伤病人的治疗作用及临床效果。方法　共 87例病人 ,随机分为亚低温治疗组和对照组。亚低温治疗组 43例 ,均于伤后 2 4小时内行亚低温治疗 ,直肠温度 (RT)控制在 31 5～ 34 9℃ ,脑温为 32 0～ 35 0℃ ,持续 1～ 7天 ,平均 5 7 7± 2 8 4小时。同时监测病人的生命体征、颅内压 (ICP)、血糖、血乳酸、血气、血电解质以及脑组织氧分压 (PbrO2 )和脑组织温度 (BT)。对照组　 44例 ,直肠温度控制在 36 5～ 37 5℃ ,其他治疗同亚低温组。两组病人均于伤后 3个月时根据GOS评估法判定疗效。结果　　与对照组相比 ,亚低温治疗组病人伤后早期的高ICP、高血糖、高乳酸血症分别显著下降 (P <0 0 5 ) ;严重的低PbrO2 迅速上升并维持在正常水平 ;生命体征、血气及血电解质无显著差异 ;无严重并发症 ,死亡率降低 ,恢复良好率提高 ,预后显著改善。结论　亚低温具有肯定的脑保护作用 ,临床上用于治疗急性重型颅脑损伤病人 ,安全有效 ,可降低死亡率 ,提高生存质量 ,无严重并发症。直接监测PbrO2 和BT ,对亚低温治疗更有指导意义     

亚低温治疗重型颅脑损伤44例临床分析

目的研究亚低温对急性重型颅脑损伤病人治疗作用及临床效果。方法共88例病人（GCS昏迷≤8分）随机分为亚低温治疗组44例，尽快采用亚低温治疗。直肠温度控制在33℃～35．5℃，持续1～7d。对照组44例，常规治疗，直肠温度控制在36．5℃～37．5℃。两组病人均于伤后3个月时根据GOS评估法判定疗效。结果与对照组相比．亚低温治疗组恢复良好率提高，病死率降低，预后显著改善，无严重并发症。结论亚低温具有肯定的脑保护作用，用于治疗急性重型颅脑损伤病人，可降低病死率，提高生存质量，无严重并发症。     

亚低温在急性颅脑损伤中的治疗意义

1 历史回顾 五十年代始,国内外神经外科曾经采用轻(33～35℃)至中度低温(28～32℃)治疗重型颅脑伤。据文献检索发现,全世界几十家医院对大约100多例重型颅脑伤采用低温治疗,多数学者都认为低温对重型颅脑伤有一定疗效,且无任何心脏和凝血系统严重并发症。由于上述均为临床个案或少量病例报道,未作前瞻性对照研究,所以无法对低温治疗重型颅     

亚低温对急性重型颅脑损伤病人治疗机理及临床疗效研究

目的研究亚低温对急性重型颅脑损伤病人的治疗机理及临床效果.方法164例病人,随机分为亚低温治疗组和对照组.亚低温治疗组82例,均于伤后24小时内行亚低温治疗,直肠温度(RT)控制在32.0℃～35.0℃;脑温为32.5℃～35.0℃,持续1～7天,平均60.2±28.0小时.同时监测病人的生命体征、颅内压(ICP)、血糖、血乳酸、血气、血电解质以及脑组织氧分压(PbrO2)和脑组织温度(BT)、脑微循环血流(LDF血流值)和颈静脉血氧饱和度(SjvO2).对照组82例,直肠温度控制在36.5℃～37.0℃,其他治疗同亚低温组.两组病人均于伤后3个月时根据GOS评估法判定疗效.结果与对照组相比,亚低温治疗组病人伤后早期的高ICP、高血糖、高乳酸血症分别显著下降(P＜0.05);严重的低PbrO2迅速上升并维持在正常水平;脑血供得到改善;生命体征、血气及血电解质无显著差异;无严重并发症;死亡率降低,恢复良好率提高,预后显著改善.结论亚低温具有肯定的脑保护作用,临床上用于治疗急性重型颅脑损伤病人,安全有效,可降低死亡率,提高生存质量,无严重并发症.直接监测PbrO2、BT、LDF血流值和SjvO2,对亚低温治疗更有指导意义.     

亚低温与重型脑损伤病人外周血NSE关系的临床研究

目的研究亚低温对重型颅脑损伤病人外周血神经元特异性烯醇化酶(NSE)的影响以及亚低温对重型颅脑损伤病人的神经保护作用。方法将24例重型颅脑损伤病人分为亚低温组(12例)和对照组(12例)。前者进行亚低温治疗,对照组不进行亚低温治疗,其它治疗措施与亚低温组相同,于术前、术后次日、术后3d、术后7d均抽取外周血测NSE含量。结果亚低温组第3d和第7d的NSE分别为(33·33±9·44)和(20·11±5·09)ng/ml,明显低于对照组(40·47±6·00)和(33·63±6·23)ng/ml(P<0·05和P<0·01)。结论通过亚低温治疗能抑制NSE的释放,对重型颅脑损伤病人的神经元细胞和神经内分泌细胞继发性损害有保护性作用,在临床上值得推广应用。     

亚低温治疗重型颅脑损伤的临床疗效观察

目的探讨亚低温疗法在颅脑损伤治疗中的作用。方法73例颅脑损伤患者分为①亚低温组：31例，均于伤后24h内接受亚低温治疗，直肠温度控制在32～34℃，维持3～7d；②常规治疗组：42例，其他治疗同亚低温组，根据GOS预后评估系统评估两组患者疗效。结果与常规治疗组相比，亚低温组患者伤后早期颅内压显著下降（P〈0．05）；生命体征、血气及电解质无显著性差异（P〈0．05）；无严重并发症，死亡率降低，恢复良好，预后显著改善。结论亚低温疗法能减轻颅脑损伤后脑水肿，降低颅内压，伤后24h内接受亚低温治疗，疗效确切，可降低颅脑损伤患者的死亡率，提高其生存质量。     

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.