利妥昔单抗治疗抗N-甲基-D-天冬氨酸受体脑炎的研究进展

抗N-甲基-D-天冬氨酸受体(N-methyl-D-aspartate receptor,NMDAR)脑炎是一种较为常见的免疫介导性脑炎,好发于18岁以下儿童。抗NMDAR脑炎可表现为进行性精神病、癫痫及自主功能障碍,若不加干预和治疗则易导致患者死亡。利妥昔单抗常用于抗NMDAR脑炎的二线免疫治疗,临床效果较为显著。本文就利妥昔单抗治疗抗NMDAR脑炎的研究进展做一综述。     

癫痫的药物治疗研究进展

抗癫痫药物治疗是癫痫临床治疗的主要方案,目前临床治疗中尚存在诸多问题。本文综述近年遗传学研究对癫痫治疗的影响、治疗药物监测、中药治疗机制以及新型抗癫痫药物开发等研究进展。     

不同发育阶段儿童癫痫的用药特点及不良反应研究进展

癫痫是儿童神经系统最常见的疾病之一,目前药物治疗仍是首选方案。儿童癫痫药物治疗与成人有所不同,对不同发育阶段的儿童的癫痫治疗需特殊考虑。婴幼儿期:脏器发育不完善,抗癫痫药物的选择应考虑其安全性;学龄前期和学龄期:学习、认知和社会心理发展的关键时期,抗癫痫药物选择应充分考虑其对认知功能的影响;青春前期和青春期:抗癫痫药物治疗要考虑其长期用药对患儿生长发育各个环节的影响。因此,本文综述了其药物治疗进展及搜集了相关的循证医学证据。     

托珠单抗治疗一例儿童难治性抗NMDAR脑炎的病例报告并文献复习

目的 探讨托珠单抗治疗一例儿童难治性抗NMDAR脑炎的安全性及有效性,为治疗该疾病提供参考。方法 回顾性分析浙江大学医学院附属儿童医院一例儿童难治性抗NMDAR脑炎的临床表现、诊治经过及应用妥珠单抗的安全性及有效性,并结合相关文献复习加以讨论。结果 该患儿应用了2次大剂量甲泼尼龙、丙种球蛋白及6次利妥昔单抗后临床症状无好转,应用6次托珠单抗后,改良Rankin量表（mRS）评分有改善,无不良反应。结论 托珠单抗作为升级的二线免疫治疗药物对难治性抗NMDAR脑炎治疗有效,耐受性好,是一种具备潜力的治疗手段之一。     

临床药师参与1例病毒性脑炎伴继发性癫痫患者的药学监护

目的:探讨临床药师在病毒性脑炎伴继发性癫痫患者治疗中的作用。方法:临床药师参与1例病毒性脑炎伴继发性癫痫患者的药物治疗过程,协助医师监测抗癫痫药物血药浓度、药物相互作用,优化抗菌药物治疗方案。治疗过程中临床药师先后建议医师停用美罗培南,更换为注射用头胞哌酮钠舒巴坦钠3 g,ivgtt,q8 h+注射用盐酸万古霉素1 g,ivgtt,q12 h抗感染;调整注射用丙戊酸钠用量为0.4 g,ivgtt,q6 h抗癫痫,并避免药物相互作用,密切监视患者生命体征;停用18种氨基酸注射液及甘油果糖等,以排除药物热。结果:医师采纳临床药师建议。经过48 d的治疗,患者病情得到了有效控制并出院。结论:临床药师参与病毒性脑炎伴继发性癫痫患者的药物治疗过程,根据血药浓度协助医师优化调整方案,可最大程度地减少药物相互作用的发生,确保临床治疗的安全、有效。     

抗N-甲基-D-天冬氨酸受体脑炎

抗N-甲基-D-天冬氨酸受体(anti-N-methyl-D-aspartate receptor,NMDAR)脑炎是与NMDAR的亚单位NR1相关的一种脑炎,其特点为病程呈多阶段性,主要表现为精神异常、记忆障碍、癫痫发作、意识水平降低等,常伴有运动障碍、自主神经功能紊乱和呼吸节律异常。     

解读“中国抗癫痫药物治疗专家共识(2011)”

抗癫痫药物(AED)是临床癫痫的主要治疗手段,合理选择个体化治疗方案是治疗的关键。本文结合近期出台的《中国抗癫痫药物治疗专家共识(2011)》中的相关治疗建议,综述AED的临床应用。     

儿童难治性癫痫的治疗进展

癫痫为临床常见儿童神经系统疾病,相较于成人癫痫患者,儿童癫痫病因与临床治疗手段、临床表现上有明显差异。癫痫发作与抗癫痫药物的大量应用,对患儿学习、生活与成长发育均造成严重困扰。传统抗癫痫药物会产生较为严重的不良反应,且难以完全治愈,患儿难以耐受。近年来,随着医疗不断发展,抗癫痫治疗也得到极大的进展,特别是对儿童难治性癫痫,其治疗手段已经获得极大突破。目前,针对儿童难治性癫痫,治疗方法较多,本文对儿童难治性癫痫的治疗进展作分析,现综述如下。     

抗癫痫药的药物经济学研究进展

癫痫为慢性发作性疾病,需长期坚持药物治疗,抗癫痫药物治疗是癫痫治疗的主要手段,并取得了良好临床疗效.治疗过程中,在保证疗效的前提下,同时如何尽可能地为病人节省费用是一大难题,故经济因素也常常影响抗癫痫药的选择.随着新型抗癫痫药物在临床中的广泛应用,为选择治疗药物提供优良备选方案和应用思路.本文旨在对抗癫痫药物进行药物经济学评价,为临床合理用药提供参考.     

抗癫痫类药物的临床应用及不良反应分析

癫痫属于一种脑部疾病,特点是持续存在能产生癫痫发作的易感性,进而出现相对应的神经生物学、心理学、认知及社会学等方面的后果。癫痫的发作严重影响了患者的智力(主要是儿童)、心理、学习等生活质量。大量文献证明,目前国内外对癫痫患者的治疗仍是以药物治疗为主,抗癫痫药物的不良反应也多种多样,应用不当,会严重影响患者的生活质量,所以分析抗癫痫药物的临床应用,解析此类药物不良反应发生的原因,寻找更好、更合理的给药方案,很有必要。本文综述了目前抗癫痫药物的临床应用状况和不良反应发生特征,剖析了不良反应发生的原因,为指导临床合理用药、避免药物不良反应的发生、提高患者的生活质量奠定基础。     

儿童抗N-甲基-D-天冬氨酸受体脑炎19例临床分析

目的:总结儿童抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎临床特点,以提高临床医师对该病的认识。方法:回顾性分析2015年12月至2017年3月于江西省儿童医院神经内科就诊的19例抗NMDAR脑炎患儿的临床表现、辅助检查、治疗、预后。结果:临床主要表现为精神行为异常、抽搐、运动障碍、睡眠障碍;10例头颅MRI异常;17例脑电图异常,主要表现为背景活动慢;5例脑脊液常规异常,淋巴细胞增高为主;2例血清抗NMDAR抗体IgG阴性,17例血清抗NMDAR抗体阳性及19例脑脊液抗体阳性;17例予一线免疫治疗,15例好转;随访16例,15例均好转,其中2例复发。结论:儿童抗NMDAR脑炎无明显性别差异,临床主要表现为精神异常、抽搐、运动障碍、睡眠障碍,出现中枢性通气障碍及合并肿瘤较少见,约半数头颅MRI表现异常,主要为颞叶受损;脑电图主要表现为背景活动慢,脑脊液无明显特异改变,少部分血清免疫抗体可为阴性;多数一线免疫治疗有效,大部分预后良好,复发率低于成人。     

Lacosamide for epileptic seizures in patients with co-morbidities and unusual presentations of epilepsy

Numerous patients who are prescribed antiepileptic drugs (AEDs) for epileptic seizures are already receiving other agents for the treatment of co-morbid conditions, which frequently occur alongside epilepsy. This raises additional clinical considerations and makes the use of AEDs with good safety profiles and fewer drug-drug interactions attractive. Second and third-generation anticonvulsant drugs are associated with fewer pharmacological interactions and improved tolerability compared with first-generation drugs. Furthermore, second and third-generation anticonvulsant drugs are associated with linear pharmacokinetic profiles and differing mechanisms of action, making them ideal for pluripathological and polymedicated patients. In this report, we highlight the efficacy of one such agent, lacosamide, in five patients with co-morbidities and unusual presentations of epilepsy, including a patient with paraneoplastic encephalitis caused by microcytic lung carcinoma, one with a brain tumour and one with Alzheimer's disease, as well as a case of catamenial epilepsy and one of refractory convulsive status epilepticus. In all patients, lacosamide was associated with a substantial reduction in seizure frequency and effective control of seizure episodes. Treatment was generally well tolerated in all patients, indicating that lacosamide is an effective treatment option for a variety of patients with epileptic seizures.     

Management of neurocysticercosis

Neurocysticercosis is a common cause of neurological disease in developing countries and a major cause of epilepsy worldwide. A unique characteristic of human neurocysticercosis is that the living parasite is very well tolerated in human brain, so symptoms and clinical disease primarily result from death of the organism and accompanying inflammatory reaction in the human CNS. Among the diverse clinical manifestations of human neurocysticercosis, seizures are the most common, but other clinical problems occur, depending upon the localisation and viability of the parasite. Although both praziquantel and albendazole are effective agents, there is controversy about their role in several forms of the disease. Systematic reviews have pointed out the limited quality of available data on therapy. At a recent international conference convened to develop guidelines for treatment of this disease, areas of consensus and disagreement on the role of antiparasitic therapy were discussed. It was clear to all that cysticercosis cannot be regarded as a single disorder; treatment needs to be modified based on the location and number of cysticerci and the host response. There was a strong consensus that there is no role for antiparasitic drugs in patients with only calcified lesions. Studies suggest that patients with single enhancing lesions will do well regardless of antiparasitic therapy. Antiparasitic drugs are contraindicated in patients with cerebral oedema (cysticercal encephalitis). Most experts strongly recommend antiparasitic therapy in patients with multiple subarachnoid cysticerci or giant cysticerci. In patients with ventricular cysticerci, endoscopic removal is the preferred therapy. However, recent evidence suggests that placement of a ventricular shunt followed by antiparasitic therapy is an acceptable alternative. Standard treatment for localization-related epilepsy is effective for seizures caused by cysticercosis. In general, seizures are easily controlled in this illness. While many controversies regarding the treatment of patients with neurocysticercosis were not resolved at the international consensus conference, participants did conclude that controlled prospective studies are required to define optimal therapy for the infection and that treatment of infected individuals must be individualised.     

一线免疫治疗抗N-甲基-D-天冬氨酸受体脑炎疗效及预后因素分析

目的:探讨一线免疫治疗抗N-甲基-D-天冬氨酸受体(NMDAR)脑炎的疗效及预后。方法:选取2012年2月至2017年2月在西安市儿童医院住院的抗NMDAR脑炎患儿63例,采用糖皮质激素联合静脉注射免疫球蛋白进行治疗,随访患儿治疗后的改良Rankin量表(mRS)评分及复发情况,采用单因素及Logistic回归分析治疗后影响患儿mRS评分及复发的危险因素。结果:采用一线免疫治疗抗NMDAR脑炎2个月后,患儿mRS评分(1.52±0.71)分,随访1年有12.98%(8/63)患儿复发。单因素分析结果显示,mRS评分与患儿首次患病年龄、伴有不自主运动、高峰mRS评分、癫痫发作、治疗起效时间有关(P<0.05),患儿复发与患儿首次患病伴有不自主运动、高峰mRS评分、癫痫发作有关(P<0.05)。Logistic回归分析显示,mRS评分的危险因素有高峰mRS评分、伴有不自主运动、癫痫发作、治疗起效时间(P<0.05);患儿复发的危险因素有高峰mRS评分和癫痫发作(P<0.05)。结论:一线免疫治疗抗NMDAR脑炎效果明确,高峰m RS评分和癫痫发作是影响患儿治疗后短期疗效及患儿复发的重要危险因素。     

卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的效果观察

目的探讨卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的临床疗效。方法选取本院2006年3月至2011年4月收治的脑炎继发癫痫患者93例,随机分为三组,采用卡马西平(300mg/d)治疗患者31例为观察Ⅰ组,采用托吡酯(起始剂量为25mg/d,每周增加25mg/d,目标剂量为100mg/d)治疗患者31例为观察Ⅱ组,采用丙戊酸钠(500mg/d)治疗患者31例为观察Ⅲ组,疗程均为1年,比较三组患者治疗后的临床疗效及不良反应情况。结果治疗总有效率由高到低分别为观察Ⅲ组(77.4%)、观察Ⅱ组(74.2%)、观察Ⅰ组(67.7%),差异均无统计学意义(P>0.05)。不良反应发生率由高到低分别为观察Ⅰ组(38.7%)、观察Ⅲ组(22.6%)、观察Ⅱ组(9.7%),差异均有统计学意义(P<0.05)。结论卡马西平、托吡酯与丙戊酸钠治疗脑炎继发癫痫的临床疗效相当,托吡酯不良反应发生率最低更适合于临床应用。     

Update on novel antiepileptic drugs

Epilepsy is the most common serious neurological condition. Approximately 20% of patients with epilepsy are resistant to current antiepileptic drugs (AEDs), and newly licensed AEDs have not significantly changed the prognosis for this group. New AEDs are thus still needed to treat this refractory group. Although established AEDs have been very successful in treating epilepsy, they are associated with frequent adverse events, and newer AEDs with better side-effect profiles may eventually replace the older drugs as first-line therapy. There has, however, been caution in using new AEDs as first-line treatment because of questions of long-term safety and cost. As well as treating epilepsy, there is a need for drugs that prevent the development of epilepsy following, for example, head injury. None of the established AEDs has been shown to achieve this, but newer drugs have been found to be anti-epileptogenic in animal models. Whether this is so in the clinical situation has yet to be established. This is a potentially large under-investigated market. Although new AEDs have largely been developed through widespread screening in animal epilepsy models and the modification of existing compounds, there has been a growth in the rational development of AEDs. Drugs that increase brain g-aminobutyric acid (GABA) concentrations have now become well-established, and a new drug, tiagabine, that operates via this mechanism is shortly to be launched in a number of countries. Research has recently been concentrated on the development of drugs whose antiepileptic effect is mediated through glutamate receptors. Initial investigation of N-methyl-D-aspartate (NMDA) receptor antagonists in patients with epilepsy was disappointing, but drugs that act via non-NMDA glutamate receptors, and metabotropic glutamate receptors look promising.     

Do antiepileptic drugs play a role in sudden unexpected death in epilepsy?

Sudden unexpected death in epilepsy (SUDEP) accounts for approximately 2% of deaths in population-based cohorts of epilepsy, and up to 25% of deaths in cohorts of more severe epilepsy. When it occurs, SUDEP usually follows a generalised tonic-clonic seizure. Unresponsiveness, apnoea, and cardiac arrest occur in SUDEP, rather than the typical gradual recovery. The great majority of tonic-clonic seizures occur without difficulty and how the rare seizure associated with SUDEP differs from others is unknown.Three mechanisms have been proposed for SUDEP: cardiac arrhythmia, neurogenic pulmonary oedema, and postictal suppression of brainstem respiratory centres leading to central apnoea. Recent studies have found that the incidence of SUDEP increases with the severity of epilepsy in the population studied. The duration of epilepsy, number of tonic-clonic seizures, mental retardation, and simultaneous treatment with more than two antiepileptic drugs are independent risk factors for SUDEP. Some studies have reported that carbamazepine use, carbamazepine toxicity, and frequent, rapid changes in carbamazepine levels, may be associated with SUDEP. Other evidence indicates that carbamazepine could potentially increase the risk for SUDEP by causing arrhythmia or by altering cardiac autonomic function. However, this evidence is tenuous and most studies have not found an association between the use of carbamazepine or any other individual antiepileptic drug and SUDEP.There is little information regarding antiepileptic drugs other than phenytoin and carbamazepine. The incidence of SUDEP with gabapentin, tiagabine, and lamotrigine clinical development programmes is in the range found in other populations with refractory epilepsy. This suggests that these individual antiepileptic drugs are no more likely to cause SUDEP than antiepileptic drugs in general.Best current evidence indicates that the risk of SUDEP can be decreased by aggressive treatment of tonic-clonic seizures with as few antiepileptic drugs as necessary to achieve complete control. At present there is no strong reason to avoid any particular antiepileptic drug. Further studies are needed to elucidate the potential role of individual antiepileptic drugs in SUDEP and establish clinical relevance, if any. These studies may be challenging to conduct and interpret because SUDEP is relatively uncommon and large numbers will be necessary to narrow confidence intervals to determine the clinical relevance. Also adjustments will be needed to account for the potent risks associated with other independent factors.     

帕金森病合并癫痫的治疗

帕金森病和癫痫均为常见的神经系统慢性疾病，但帕金森病合并癫痫在临床上较为少见，部分研究显示帕金森病患者癫痫发作风险增加。脑深部电极刺激术为帕金森病外科治疗的主要选择，但其并发症包括癫痫发作，与较高的发病率和死亡率有关。此外，帕金森合并癫痫患者认知障碍风险增加，一线治疗药物胆碱酯酶抑制剂存在着诱发或加重癫痫发作的可能，而唑尼沙胺是目前唯一可用于帕金森病治疗的抗癫痫药物。本文就帕金森病合并癫痫患者治疗过程中的关键问题进行阐述，以期为临床治疗提供参考。     

多药耐药机制与难治性癫痫关系的研究进展

难治性癫痫是多年来困扰临床医生的常见问题，其重要特征是大部分患者对许多抗癫痫药物抵抗，尽管这些药物有不同作用机制，说明这种现象可能由非特异性机制所介导。本文对难治性癫痫近年来有关多药耐药现象进行综述。     

Drug treatment of microsporidiosis

Microsporidia are ubiquitous organisms that are emerging pathogens in humans. These are most likely zoonotic and/or waterborne infections. In the immunosuppressed host, such as those treated with immunosuppressive drugs or infected with human immunodeficiency virus particularly at advanced stages of the disease, microsporidia can produce a wide range of clinical diseases. The most common manifestation is gastrointestinal tract infection; however, encephalitis, ocular infection, sinusitis, myositis and disseminated infection have also been described. In addition, these organisms have been reported in immune competent individuals. Multiple genera are involved in these infections and different organisms can result in distinct clinical pictures. Differences in clinical and parasitologic response to various therapeutic agents have emerged from clinical, as well as in vitro and in vivo studies. Currently there are no precisely defined guidelines for the optimal treatment of microsporidial infections. This article reviews the available data on compounds with in vitro activity and/or in vivo efficacy for microsporidial infections.