汉族人拉莫三嗪相关过敏反应与HLA-B*1502的相关性

目的研究在汉族人中拉莫三嗪相关过敏反应是否与HLA-B*1502有相关性。方法对在郑州人民医院诊断为癫痫的患者在服用拉莫三嗪前进行HLA-B*1502测定,将服用拉莫三嗪12周后出现过敏反应者作为实验组,未出现过敏反应者作为对照组1,服用其他非芳香族抗癫痫药物出现过敏反应者为对照组2,检测对照组2的HLA-B*1502阳性率,对3组间HLA-B*1502的阳性率进行比较。结果实验组HLA-B*1502的阳性率为41.86%,对照组1为14.02%,对照组2为13.33%.实验组阳性率高于对照组1(χ2=13.86,P<0.05)及对照组2(χ2=6.83,P=0.009),对照组1与对照组2比较差异无统计学意义(χ2=0.009,P=0.924)。结论HLA-B*1502可能与汉族人拉莫三嗪相关过敏反应相关。     

抗癫痫药物皮肤不良反应与HLA-B*1502基因关联性研究

目的 研究抗癫痫药物引致的皮肤不良反应和人白细胞抗原HLA-B*1502基因的关联性.探讨抗癫痫药物的个体化治疗. 方法 广州医学院第二附属医院癫痫门诊自2007年1月至2008年5月共收治癫痫患者31例.其中应用卡马两平(CBZ)引致皮肤不良反应13例[Stevens-Johnson综合征(SJS)6例、轻度斑丘疹(MPE)7例],无皮肤不良反应15例,应用拉莫三嗪(LTG)引致MPE 3例.采用顺序特异性引物聚合酶链反应(PCR-SSP)检测以上患者和未服用过CBZ或LTG的30例正常对照者的HLA-B*1502基因分型. 结果 HLA-B*1502基因型阳性例数和基因频率分别为:CBZ引致SJS组6例(6/6,100%),CBZ引致MPE组4例(4/7,57%),LTG引致MPE组I例(1/3,33%),无皮肤不良反应组1例(1/15,7%),正常对照组3例(3/30,10%).CBZ引致SJS组、CBZ引致MPE组患者HLA-B*1502基因型阳性率均高于正常对照组和无皮肤不良反应组,差异均有统计学意义(P<0.05). 结论 CBZ导致的皮肤不良反应与HLA-B*1502基因型有关.     

癫痫患者脑组织中SCG10的表达与耐药性的相关性分析

目的对癫痫患者脑组织中SCG10的表达进行分析,并探讨其与耐药的相关性。方法选取40例耐药性癫痫患者为观察组,40例神经外科减压或清创治疗的患者为对照组,对2组的SCG10表达进行观察,并分析其与耐药的相关性。结果观察组患者血清内SCG10水平明显大于对照组(P0.05);MAPK水平亦明显高于对照组(P0.05)。免疫荧光双标法显示SCGl0和MAPK表达在同一表达上。结论癫痫患者脑组织中SCG10的表达水平明显较高,通过对其观察能够明确患者病情,而SCG10及MAPK相互作用与疗效有一定相关性。     

新疆维吾尔族癫痫儿童卡马西平致过敏反应与HLA-B~* 1502基因型的相关性

目的探讨新疆阿克苏地区维吾尔族癫痫儿童中卡马西平所致的不良反应与HLA-B*1502等位基因型的相关性。方法收集我院2017年1月至2019年12月住院或门诊选用卡马西平单药治疗的维吾尔族癫痫儿童患者100例,将服用卡马西平后2周内出现过敏反应的3例作为观察组,未出现过敏反应的97例作为对照组,采用聚合酶链反应-直接测序分型法进行HLA-B*1502等位基因型测定。结果观察组HLA-B*1502等位基因型阳性率为0。对照组HLA-B*1502等位基因型阳性率为1.03%,基因频率0.005。两组差异无统计学意义(χ~2=0.031,P=1.000)。结论阿克苏地区维吾尔族癫痫儿童患者中,卡马西平引起过敏反应发生率较低,皮肤不良反应属于轻型过敏性皮疹,且未发现与HLA-B*1502基因型有关。     

MRP与癫痫耐药相关性研究进展

癫痫(Epilepsy)是一种脑部疾患,其特点是持续存在能产生癫痫发作的脑部持久性改变,并出现相应的神经生物学、认知、心理学以及社会学等方面的后果.我国癫痫年患病率约28.8/10万,年新增癫痫患者约38万[1].经正规的抗癫痫药(antiepileptic drugs,AEDs)治疗后,大约70％的癫痫患者发作可以控制,但仍有30％的患者对各种AEDs不敏感,成为耐药性癫痫.我国的耐药性癫痫患者至少在150万以上[2,3].耐药性癫痫患者癫痫发作频繁,严重影响了患者的生活质量,易发生癫痫持续状态,致残率和致死率高.     

癫痫与糖尿病的相关性研究进展

随着糖尿病(Diabetes mellitus,DM)和癫痫患病率的不断增加,两者共病的现象已不少见,且大量流行病学调查显示,DM和癫痫存在相关性.目前,国内外对于癫痫共病DM的认识仍不充分.本文就流行病学、基因层面、DM促进癫痫发病的机制以及两者分别与相关疗法或药物之间的关系等方面对癫痫和DM的相关性展开综述,并总结...     

胶质瘤相关性癫痫瘤组织中高迁移率族蛋白B1表达与痫性发作

目的探讨胶质瘤相关性癫痫患者瘤组织中高迁移率族蛋白B1(High-mobility group box-1,HMGB1)的表达。方法利用免疫组化半定量法检测82例胶质瘤相关性癫痫患者(胶质瘤并癫痫组)胶质瘤组织、80例胶质瘤不伴发癫痫的患者(胶质瘤非癫痫组)胶质瘤组织、80例难治性癫痫患者(非肿瘤癫痫组)致痫灶组织、20例行颅内减压术患者(阴性对照组)的正常脑组织中HMGB1的表达情况,统计分析实验组中HMGB1的表达及其临床意义。结果胶质瘤并癫痫组胶质瘤组织中HMGB1表达高于胶质瘤非癫痫组中胶质瘤组织(χ2=16.944,P0.001),低级别胶质瘤尤甚;高于非肿瘤癫痫组中致痫灶组织(χ2=26.094,P0.001)。胶质瘤非癫痫组胶质瘤组织中HMGB1的表达(χ2=32.273,P0.001)、非肿瘤癫痫组致痫灶组织中HMGB1的表达(χ2=22.236,P0.001)均高于阴性对照组中正常脑组织。胶质瘤并癫痫组中HMGB1的表达与胶质瘤相关性癫痫的持续时间(r=0.365,P=0.001)、发作频率(r=0.531,P0.001)、胶质瘤的病理级别(r=0.265,P=0.016)呈正相关。结论 HMGB1在胶质瘤相关性癫痫患者胶质瘤组织中高表达,且与癫痫发作情况关系密切,胶质瘤组织中HMGB1可能与其相关性癫痫的形成有关。     

MDR1基因多态性与癫痫性脑病耐药相关性研究

目的 探讨多药耐药基因1(MDR1)单核苷酸多态性与癫痫性脑病耐药的相关性.方法 收集2015年12月至2018年3月就诊的癫痫性脑病患儿71例及药物敏感患儿75例,应用PCR技术及DNA测序方法对rsl922242、rs2235048、rs10808072、rs868755、rsl202184单核苷酸位点进行基因分型...     

脑微出血与脑卒中相关性的临床研究

目的通过核磁共振T2*加权梯度回波成像(MRI GRE-T2*WI)筛查脑微出血(CMB),探讨CMB与卒中发生、发展之间的关系,及其与卒中危险因素之间的联系。方法纳入脑血管病患者140例,其中腔隙性脑梗死组58例、脑梗死组42例,脑出血组40例;另收集同期30例住院或门诊非血管病患者作为对照组。登记所有患者血压、血脂、血糖、既往史等基线资料,行MRI GRE-T2*WI扫描,记录各组脑微出血发生例数、部位、数目,进行统计分析。结果所有170例患者中,CMB患者的血压、血脂、血糖等较无CMB患者高,症状明显,对比明确(P均<0.05);各脑卒中组的CMB发生率均明显高于对照组(P均<0.05);各脑卒中组CMB分级构成不同(P<0.05),脑出血组CMB重度发生率明显高于其它各组;有CMB的各脑卒中组CMB总体均数比较,自发性脑出血组>腔隙性脑梗死组>脑梗死组。结论高血压病、糖尿病、高脂血症是影响CMB发生的显著因素;CMB作为微出血病变,在预测脑出血病变方面具有一定意义,可通过对CMB的诊断了解脑部出血的部位等基本信息,为以后的治疗带来方便;MRI GRE-T2*WI扫描的诊断方法为脑出血病变的常规诊断方法,此种方法在诊断脑出血病变准确度高,优势明显,因此,对于临床的诊断治疗具有显著的价值,可推广。     

血清硫化氢水平与小儿热性惊厥转为癫痫的相关性分析

目的探讨血清硫化氢(H_2S)水平与小儿热性惊厥及转为癫痫的相关性。方法选取2018年5月至2019年5月我院收治的108例小儿热性惊厥患儿,1年内转为癫痫的27例患儿纳入癫痫组,剩余81例患儿纳入热性惊厥组。选取同期体检健康的86名健康儿童作为健康对照组。检测三组血清H_2S水平,分析其与小儿热性惊厥转为癫痫的相关性。结果癫痫组患儿血清H_2S水平显著低于热性惊厥组和健康对照组(均P0.05)。小儿热性惊厥患儿血清H_2S水平变化与惊厥发作持续时间密切相关,惊厥发生前高热持续时间≥1 h的患儿血清H_2S水平显著低于惊厥发生前高热持续时间1 h的患儿,惊厥发作持续时间15 min的患儿血清H_2S水平显著低于惊厥发作持续时间≤15 min的患儿(均P0.05)。108例小儿热性惊厥患儿1年内癫痫转化率为25.00%。癫痫组与热性惊厥组间年龄、初发惊厥时体温、惊厥发生前高热持续时间、惊厥发作持续时间、合并围生期异常、合并颅脑影像异常、首次发热惊厥1周后EEG异常及血清H_2S水平的差异均有统计学意义(均P0.05)。多因素Logistic回归分析结果显示,血清H_2S水平不是小儿热性惊厥转为癫痫的独立影响因素(P0.05)。Pearson相关分析结果示,血清H_2S水平与小儿热性惊厥转为癫痫呈负相关(r=-0.637,P=0.012)。结论血清H_2S水平越低,小儿热性惊厥及转为癫痫的可能性越大。     

Association between HLA-B*1502 allele and antiepileptic drug-induced cutaneous reactions in Han Chinese

A previous study conducted in Taiwan found a 100% association between HLA-B*1502 allele and carbamazepine-induced Stevens-Johnson syndrome (SJS) in Han Chinese subjects, with an extremely high odds ratio compared with carbamazepine-tolerant subjects (odds ratio = 2,504). We examined this association in 24 Hong Kong Han Chinese subjects who had cutaneous adverse reactions induced by different antiepileptic drugs (AEDs). They were matched with 48 AED-tolerant controls. HLA-B*1502 was associated with severe cutaneous reactions (SCR) induced by AEDs, which included carbamazepine, phenytoin, and lamotrigine (p = 0.001, odds ratio = 17.6), but was not associated with maculopapular exanthema (MPE) (p = 0.32). Further studies in larger samples of ethnically matched subjects should be conducted to confirm the findings. Identification of genetic polymorphisms predisposing to development of AED-induced SCR offers the possibility of avoiding these high-risk drugs in genetically susceptible individuals.     

Association study of lamotrigine-induced cutaneous adverse reactions and HLA-B*1502 in a Han Chinese population

Antiepileptic drugs including lamotrigine (LTG) and carbamazepine (CBZ) are among the most common causes of cutaneous adverse reactions (cADRs). Human leukocyte antigen (HLA)-B*1502 has been strongly associated with CBZ-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN). To investigate this relationship, we performed high-resolution HLA genotyping on LTG-tolerant controls, healthy volunteers, and patients affected by LTG-induced cADRs, ranging from maculopapular exanthema (MPE) to SJS/TEN. Patients with LTG-induced cADRs (n=25, including three with SJS/TEN and 22 with MPE), 21 LTG-tolerant controls, and 71 healthy volunteers were enrolled. The differences in the starting dosage of LTG among the SJS/TEN, MPE, and LTG-tolerant control groups were not statistically significant. HLA-B*1502 frequency was 33.3% (1/3; LTG-induced SJS/TEN group), 9.1% (2/22; LTG-induced MPE group), 4.8% (1/21; LTG-tolerant group), and 8.5% (6/71; healthy volunteers). There was no significant difference in the frequency of subjects with the HLA-B*1502 allele between the SJS/TEN group and LTG-tolerant group (p=0.239, OR=10.0, 95% CI 0.44-228.7), and healthy volunteers (p=0.26, OR=5.42, 95% CI 0.43-68.8), MPE and LTG-tolerant groups (p=1.0, OR=1.08, 95% CI 0.20-5.8), and healthy volunteers (p=1.0, OR=2.0, 95% CI 0.17-23.9). None of the HLA alleles detected were associated with LTG-induced cADRs. In conclusion, HLA-B*1502 and other HLA alleles are not directly associated with LTG-induced MPE. The possibility that HLA-B*1502 is associated with an increased risk of LTG-induced SJS/TEN could not be excluded.     

Multi-institutional study on the correlation between chromosomal abnormalities and epilepsy

While there is an abundance of literature describing the association of chromosome aberrations with epilepsy, only a few refer to the detailed features of epilepsy. It is important to investigate the associations between specific chromosome abnormalities and features of epilepsy to identify genes involved in epilepsy and treat them more effectively. We investigated the correlation between specific chromosome aberrations and epilepsy by sending questionnaires to the members of Kyoto Multi-institutional Study Group of Pediatric Neurology. Seventy-six patients were collected from 10 institutions. Chromosome abnormalities included: Down syndrome (n = 19); Angelman syndrome (n = 8); Prader-Willi syndrome (n = 4); 4p- syndrome (n = 3); 1q- syndrome (n = 2); 5p- syndrome (n = 2); Miller-Dieker syndrome (n = 2); 18q- syndrome; (n = 2); Klinefelter syndrome; (n = 2); and 32 other individual chromosomal aberrations. Overall, the severity of mental retardation correlated with the severity of epilepsy. We could abstract characteristic features of epilepsy in some syndromes. In Angelman and Prader-Willi syndromes, febrile seizures occurred frequently, the onset of epilepsy was in early childhood and seizure phenotype was multiple. Paroxysmal discharge of the occipital region and diffuse high voltage slow wave on electroencephalography were characteristic in Angelman syndrome. In Down syndrome, West syndrome and focal epilepsy were common and the prognosis of epilepsy in West syndrome with Down syndrome was good. In 4p- syndrome, febrile seizures were often seen, and unilateral or generalized clonic or tonic-clonic status epilepticus were characteristic. For the other chromosomal aberrations investigated here, the patient numbers were too small to abstract common features of epilepsy.     

Perspectives on interactions between antiepileptic drugs (AEDs) and antimicrobial agents

In the treatment of seizures and epilepsy associated with central nervous system (CNS) infections, drug–drug interactions may significantly and unexpectedly impact outcome not only of epilepsy but also of the infectious disorders in both emergent and chronic care situations. A case is described in whom, the administration of the antimicrobial agent, meropenem presumably reduced serum valproate concentrations resulting in impaired seizure control. Other situations are reviewed in which interactions between antiepileptic drugs (AEDs) and antimicrobial agents may be of clinical significance. These include: (1) seizure management in individuals with neurocysticercosis, (2) management of seizures in patients with lobar tuberculomas, (3) management of seizures due to cerebral abscess, and (4) management of seizures in HIV-seropositive individuals.     

DRB1*1502-DQB1*0601-DQA1*0103 and DRB1*04-DQB1*0302 in Jewish hypersomnolent patients

OBJECTIVES: Narcolepsy is a sleep disorder with a genetic association with the haplotype DRB1*1501, DQA1*0102, DQB1*0602. This haplotype has been described in different ethnic groups suffering from narcolepsy (Japanese, Caucasian, African Americans, Jews). In a recent study we have found the haplotype DRB1*1502, DQB1*0601, DQA1*0103 in three patients with hypersomnolence. The similarity of this haplotype to the narcoleptic haplotype DRB1*1501, DQB1*0602 and DQA1*0102 has raised the question of whether this haplotype is a marker for sleepiness, or rather indicates a variant of non-cataplectic narcolepsy. This study was conducted to further investigate this question. METHODS: HLA-DNA analysis was carried out in 20 healthy Jewish patients (age 23.9+/-6.3 years; 13 Ashkenazi, seven non-Ashkenazi) who had objective measures of hypersomnolence. All underwent whole-night polysomnography, multiple sleep latency test and tissue typing. RESULTS: HLA-DNA analysis revealed HLA-DR2 in eight patients of whom five (25%) carried the haplotype DRB1*1502, DQB1*0601, DQA1*0103 (vs. 1.4% in the Israeli population, P<0.0001). Six patients were diagnosed as non-cataplectic narcoleptics. Five of them carried the haplotype DRB1*1502, DQB1*0601, DQA1*0103. Forty percent of the patients carried the haplotype DRB1*04, DQB1*0302, which was not statistically different from its prevalence in the healthy Israeli population (25%). CONCLUSIONS: This is the first report describing the haplotype DRB1*1502, DQB1*0601, DQA1*0103 in narcoleptic patients (non-cataplectic). This haplotype is close but different from the already known narcoleptic haplotype DRB1*1501, DQA1*0102, DQB1*0602. We assume that this haplotype represents a variant of non-cataplectic narcolepsy rather than association with hypersomnolence. However, in order to conclude whether this haplotype is a marker for the lack of cataplexy, or represents a variant of non-cataplectic narcolepsy, a larger group of patients should be investigated.     

睡眠障碍与进展性脑卒中的相关性研究

目的探讨睡眠障碍与进展性脑卒中之间的相关性,为进展性脑卒中的预测及预防提供科学的依据。方法连续选取116例卒中发作48h内的缺血性脑卒中患者,对所有患者均采用美国国立卫生研究院卒中量表(NIHSS)及SPIEGEL睡眠量表进行评分,根据NIHSS评分的变化分为进展组和非进展组,对2组患者的平均SPIEGEL评分结果进行统计学分析,并对进展组患者的平均SPIEGEL评分与NIHSS评分变化进行Pearson相关分析。结果 116例缺血性脑卒中患者中,36例病情出现进展,发生率31.03%。平均SPIEGEL评分在进展组与非进展组之间比较差异有统计学意义(P0.05),Pearson相关分析显示进展组患者平均SPIEGEL评分与NIHSS评分变化之间呈正相关。结论睡眠障碍是进展性脑卒中的危险因素,且睡眠障碍越严重,脑卒中进展越明显。     

MRP1基因表达与耐药性癫痫的相关性研究

目的研究MRP1基因表达与耐药性癫痫的相关性。方法选取90例符合诊断标准的癫痫患者,其中药物敏感患者50例,癫痫耐药患者40例。采用实时荧光定量PCR方法检测癫痫患者外周血中MRP1基因mRNA的表达水平。结果耐药性癫痫组MRP1基因mRNA表达量(9.52±1.38)高于药物敏感组(1),差异有统计学意义(P<0.05)。结论癫痫患者外周血中MRP1的表达水平,可作为诊断耐药性癫痫的参考指标。