Two novel mutations in NOTCH3 gene causes cerebral autosomal dominant arteriopathy with subcritical infarct and leucoencephalopathy in two Chinese families

Objective: To investigate the genetic pathogenic causes of cerebral autosomal dominant arteriopathy with subcritical infarct and leucoencephalopathy (CADASIL) in two Chinese families, to provide the molecular basis for genetic counseling and antenatal diagnosis. Methods: The genetic mutation of gene NOTCH3 of propositus and family members was analyzed in these two CADASIL families by polymerase chain reaction and DNA sequencing technology directly. At the same time, the NOTCH3 gene mutation point of 100 healthy collators was detected, to explicit the pathogenic mutation by function prediction with Polyphen-2 and SIFT. Results: Both propositus of the two families and patients with symptom were all accorded with the clinical features of CADASIL. It was shown by DNA sequencing that the 19^th exon [c. 3043 T > A (p.Cys1015Ser)] in gene NOTCH3 of propositus, 2 patients (II3, III7), and a presymptomatic patient (IV1) in Family I all had heterozygosity missense mutation; and the 3^rd exon [c.316T > G, p. (Cys106Gly)] in gene NOTCH3 of the propositus, a patient (IV3) and two presymptomatic patients (IV5, 6) in Family II all had heterozygosity missense mutation; and no mutations were detected in the 100 healthy collators. It was indicated by analyzing the function prediction that the mutation of [c. 3043 T > A (p.Cys1015Ser)] and [c.316T > G, p. (Cys106Gly)] may both influence encoding protein in NOTCH3. By analysis of the conservatism of mutation point in each species, these two basic groups were highly conserved. Conclusion: The heterozygosity missense mutation of 19^th exon [c. 3043 T > A (p.Cys1015Ser)] and the 3^rd exon [c.316T > G, p. (Cys106Gly)] in NOTCH3 gene are the new pathogenic mutations of CADASIL, and enriches the mutation spectrum of NOTCH3 gene.     

人脐血间充质干细胞移植与神经节苷脂注射治疗脑瘫大鼠的对比研究

目的：建立稳定的人脐血间充质干细胞（mesenchymal stem cells,MSCs）分离培养体系,观察其移植对脑瘫(CP)大鼠功能恢复的影响及细胞的存活、迁移、向神经细胞分化的情况,并与神经节苷脂（GM1）注射对CP鼠神经功能恢复进行对比。方法：采集足月新生儿脐带血100ml,分离出单个核细胞,体外培养并予5 溴脱氧嘧啶尿苷（Brdu）标记72h;受孕17d孕鼠腹腔注射脂多糖（LPS）0.4mg/(kg·d),12h后置于缺氧环境2～2.5h,4h后再次腹腔注射同剂量LPS,孕鼠自体分娩,生后4周,通过行为学评分选择CP模型动物80只,随机分为4组：CP组（CP模型）、假移植组（CP模型+PBS）、MSCs移植组（CP模型+MSCs）、GM1注射组（CP模型+GM1）,每组20只。移植后第1、2、3周应用免疫荧光法观察Brdu标记的MSCs的存活、迁移,移植后第4周,通过行为学评价观察大鼠神经功能恢复情况,应用免疫荧光法检测其胶质纤维酸性蛋白(GFAP)和神经元特异性烯醇化酶（NSE）的表达情况。结果：MSCs移植比GM1注射使大鼠握持时间更长,足错误次数更少(P<0.05);移植的MSCs可在大鼠脑组织中存活, 并向四周脑组织迁移, (0.45±0.68)个MSCs表达GFAP,(0.15±0.36)个MSCs表达NSE。结论：人脐血MSCs移植比神经节苷脂注射较好的提高CP大鼠神经功能的恢复, 移植细胞可在大鼠脑缺血区域中存活、迁移,并部分向星形胶质细胞或神经元分化。     

体外冲击波治疗脑瘫肌痉挛的疗效观察

目的:观察体外冲击波对脑瘫患儿小腿三头肌痉挛的疗效和安全性。方法:脑瘫肌痉挛患儿50例分为观察组24例和对照组26例,2组均给予常规康复治疗,观察组加用冲击波治疗,治疗前后对2组患儿的被动关节活动度(PROM)、改良的Asworth分级(MAS)、粗大运动功能评分(GMFM)、足底支持面积和足底压力进行评定。结果:观察组治疗1周及4周后,小腿三头肌MAS评分较治疗前明显下降(P<0.05),且呈逐渐下降趋势(P<0.05),且各时间段各项评分均更低于对照组(P<0.05);对照组治疗1周后,小腿三头肌MAS评分及踝关节PROM与治疗前比较差异无统计学意义,治疗4周后,小腿三头肌MAS评分较治疗前及治疗1周时明显下降(P<0.05)。观察组治疗1周及4周后,踝关节PROM、GMFM评分、足底面积及足底压力均较治疗前明显增加(P<0.05),且呈逐渐上升趋势(P<0.05),且各时间段各项评分均更高于对照组(P<0.05);对照组治疗1周后,踝关节PROM、GMFM评分、足底面积及足底压力与治疗前比较差异无统计学意义,治疗4周后,踝关节PROM、GMFM评分、足底面积及足底压力均较治疗前及治疗1周时明显增加(P<0.05)。结论:体外冲击波治疗可以降低脑瘫患儿小腿三头肌张力,缓解肌肉痉挛,改善其粗大运动功能。     

鼻咽通气道在急重症脑动脉瘤栓塞术患者恢复期的应用

目的：观察恢复期早期拔除气管导管并置入鼻咽通气道对预防急重症脑动脉瘤栓塞术患者拔管期不良反应的效果。方法60例急诊行脑动脉瘤栓塞术的患者,GCS评分8～10分,ASAⅢ～Ⅳ级,随机分为鼻咽通气道组（ A组）、口咽通气道组（ B组）和手托下颌组（ C组）,每组20例。记录三组患者拔除气管导管前（ T0）、置入鼻／口咽通气道（ C 组手托下颌）后1 min （ T1）、5 min（ T2）、10 min（ T3）和20 min（ T4）的SpO2、HR、SBP、DBP、PaCO2、血浆肾上腺素（ E）及去甲肾上腺素（ NE）浓度（桡动脉血）,并观察拔管后20 min内的不良反应包括呛咳、躁动、恶心呕吐及喉痉挛等。结果 T1时B组HR、SBP、DBP、PaCO2、血浆E及NE浓度高于A组和C组（ P＜0.05）,A组HR、SBP、DBP、PaCO2、血浆E及NE浓度略高于C 组,但差异无统计学意义（ P＞0.05）;T2、T3、T4时B组和C组HR、SBP、DBP、PaCO2、血浆E及NE浓度高于A组（P＜0.05）。 A组不良反应发生率明显低于B组和C组（P＜0.05）。结论鼻咽通气道应用有利于急重症脑动脉瘤栓塞术患者全麻苏醒期,可有效地保持患者呼吸道通畅并减轻患者拔管期的不良反应。     

Correlation between biochemical indicators of blood lipid with cerebral vascular diseases

Objective: The objective of this study was to investigate correlation of the changes in serum levels of cholesterol (chol), lipoprotein (a) (Lpa) and homocysteine (HCY) with incident cerebral infarction and cerebral hemorrhage. Methods: Data on a total of 418 patients (318 cerebral infarction events and 100 cerebral hemorrhage cases) were analyzed in this study. Serum chol and HCY levels were tested by means of GPO-PAP. Serum Lpa levels were measured using latex agglutination turbidimetry. Results: Patients with cerebral infarction showed significantly higher serum Lpa levels and anomaly ratio than those with cerebral hemorrhage (P < 0.05), while no significant changes were identified for chol and HCY (P > 0.05). Analyses by age indicated substantially increased Lpa concentration among cerebral infarction patients > 60 years of age (P < 0.05). No statistical significance was observed in other analyses carried out in the study. Conclusion: These results demonstrate that Lpa concentration is clearly correlated with cerebral infarction incidence. Lpa may act as an independent risk factor and could be used as a biomarker for this disease.     

改良Ashworth量表与改良Tardieu量表在痉挛型脑瘫患儿评定中的信度研究

目的:检验改良Ashworth量表(MAS)与改良Tardieu量表(MTS)评定脑瘫(CP)儿童肢体痉挛时评定者间的信度。方法:共收集20例痉挛型脑瘫患儿,其中8例为偏瘫型脑瘫,12例为双瘫型脑瘫,30个痉挛下肢,分别由两名治疗师使用MAS与MTS对患儿患侧下肢痉挛的腘绳肌、踝跖屈肌群进行测量,以检验MAS与MTS的评定者间的信度。结果:MAS在腘绳肌和踝跖屈肌群的评定者间信度较低(kappa值为0.379—0.436);而MTS的肌肉反应特性X评定者间信度较好(kappa值为0.653—0.829);而各角度测量的评定者间信度的ICC值(除腘绳肌R2-R1外)均大于0.75,且在95%置信区间集中(P0.001)。结论:MTS在脑瘫下肢的应用信度较好,能较好地反映肌肉痉挛情况,有较好的临床价值,而MAS量表在痉挛型脑瘫儿童下肢肢体痉挛评定的信度较低,临床中应用于疗效评定时需谨慎。     

成人脑瘫患者6分钟步行试验步行距离的影响因素

目的:探究在成人脑瘫患者中不同生理因素及粗大运动功能对6min步行试验步行距离(6MWD)的影响。方法:将符合脑瘫诊断标准的55例患者纳入研究,分别测定身高(height)、体重(weight)、静息状态下的心率(RHR)和血压(BP),并使用粗大运动功能测定量表(GMFM)评定患者粗大运动功能总分(GMFM总),以及D和E功能区的分数(分别记为GMFM-D、GMFM-E),然后进行6min步行试验(6MWT),测定患者步行试验过程中的摄氧量(VO2总)、心率(HR步)以及6MWD,并计算出步行5m的速度(speed 5m)、每公斤体重摄氧量(VO2/kg)和步行每米摄氧量(VO2/m)。结果:成人脑瘫患者6MWD相关的因素主要包括RHR(r=-0.531,P0.05),VO2/m(r=-0.542,P0.05),VO2/kg(r=0.682,P0.001)、GMFM总(r=0.614,P0.01)、GMFM-D(r=0.538,P0.05)、GMFM-E(r=0.679,P0.001)和speed 5m(r=0.680,P0.001),其中GMFM-E(r=0.679,P0.001)、VO2/kg(r=0.682,P0.001)和speed 5m(r=0.680,P0.001)对6MWD具有显著影响,而height(r=0.01,P=0.81)、6MWT的HR(r=0.04,P=0.68)及BP(r=0.16,P=0.50)与6MWD结果无显著关联。结论:步行相关的粗大运动功能以及步行过程中有氧代谢水平是影响成人脑瘫患6MWD的主要因素。     

手术夹闭与介入栓塞治疗对后交通动脉瘤动眼神经麻痹恢复的疗效比较

目的：比较手术夹闭与介入栓塞治疗后交通动脉瘤伴动眼神经麻痹的临床疗效。方法回顾性分析2005年10月至2009年10月后交通动脉瘤伴动眼神经麻痹患者68例的临床资料,其中手术夹闭治疗43例（夹闭组）,介入栓塞治疗25例（栓塞组）。结果治疗后两组患者眼裂均增大,瞳孔缩小,与治疗前比较差异有统计学意义（P<0.05）,但夹闭组改善幅度更大,两组比较差异有统计学意义（P<0.05）。随访6个月,夹闭组患者动眼神经麻痹完全恢复34例（79.07%）、部分恢复8例（18.60%）、未恢复1例（2.33%）;栓塞组患者完全恢复13例（52.00%）、部分恢复10例（40.00%）、未恢复2例（8.00%）,差异有统计学意义（P<0.05）。夹闭组完全恢复时间（30.90±5.47）d,短于栓塞组的（47.83±6.62）d,差异有统计学意义（P<0.05）。结论手术夹闭治疗后交通动脉瘤伴动眼神经麻痹的临床效果优于介入栓塞治疗,值得临床推广应用。