目的 观察癫痫患儿规范应用抗癫痫发作药物(antiseizure medications,ASMs)或联合糖皮质激素治疗后低纤维蛋白原血症发生情况及严重程度,探讨抗癫痫治疗后发生低纤维蛋白原血症的因素和治疗结局.方法 33例应用ASMs或联合糖皮质激素规范治疗后发生低纤维蛋白原血症的癫痫患儿,确诊低纤维蛋白原血症后给予人纤维蛋白原、必要时降低丙戊酸钠药物剂量等治疗.记录癫痫发作类型、综合征类型、病因、治疗后发生低纤维蛋白原血症的中位时间、发生低纤维蛋白原血症时的治疗方案;于抗癫痫治疗前、诊断低纤维蛋白原血症时、低纤维蛋白原血症治疗次日及治疗后1个月检测纤维蛋白原(fibrinogen,Fib)、凝血酶原时间、凝血酶时间、活化部分凝血活酶时间、纤维蛋白降解产物、D-二聚体、中性粒细胞计数、白细胞计数、血红蛋白、血小板计数.随访至2022年8月,观察患儿低纤维蛋白原血症复发情况.结果 33例发作类型为痉挛发作24例,强直-阵挛发作6例,强直痉挛发作2例,肌阵挛发作1例;婴儿癫痫性痉挛综合征21例;病因不明14例,结构性病因13例,遗传性病因6例;1例因不易止血发现且合并轻度肝功能损伤,余32例在随访期间常规检测血常规、凝血功能时发现.诊断低纤维蛋白原血症时,33例中32例应用丙戊酸钠,其中26例(含21例婴儿癫痫性痉挛综合征)应用糖皮质激素联合丙戊酸钠等ASMs,1例应用糖皮质激素联合左乙拉西坦、托吡酯及氯硝西泮,6例未应用糖皮质激素(5例应用丙戊酸钠联合其他ASMs,1例单用丙戊酸钠).诊断低纤维蛋白原血症时Fib水平[0.930(0.850,0.980)g/L]低于抗癫痫治疗前[2.460(2.140,2.675)g/L](Z=-5.013,P＜0.001),凝血酶时间[(20.676±1.756)s]长于抗癫痫治疗前[(18.284±1.605)s](t=7.478,P＜0.001),活化部分凝血活酶时间[(34.803±5.446)s]短于抗癫痫治疗前[(40.447±5.402)s](t=-6.030,P＜0.001).31例诊断低纤维蛋白原血症时Fib水平＜1.0 g/L,静脉滴注人纤维蛋白原,30例应用丙戊酸钠者同时口服左卡尼汀,次日低纤维蛋白原血症纠正;2例诊断低纤维蛋白原血症时Fib水平为1.0 g/L,口服左卡尼汀并降低丙戊酸钠剂量后低纤维蛋白原血症得到纠正.33例低纤维蛋白原血症治疗次日Fib水平[1.950(1.515,2.490)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶原时间[(12.564±1.140)s]、凝血酶时间[(17.491±1.515)s]均短于诊断低纤维蛋白原血症时[(13.752±1.591)、(20.676±1.756)s](P＜0.05);低纤维蛋白原血症治疗1个月Fib水平[1.550(1.390,1.659)g/L]高于诊断低纤维蛋白原血症时(P＜0.05),凝血酶时间[(17.680±1.465)s]短于诊断低纤维蛋白原血症时(P＜0.05),活化部分凝血活酶时间[(37.601±5.728)s]长于诊断低纤维蛋白原血症时(P＜0.05).中位随访32.75(24.90,43.88)个月,1例间隔2个月再次发生低纤维蛋白原血症,再次静脉滴注人纤维蛋白原并降低丙戊酸钠剂量后纠正,余患儿未再发生低纤维蛋白原血症.结论 应用丙戊酸钠或联合糖皮质激素治疗、发作类型为婴儿癫痫性痉挛综合征的癫痫患儿易发生低纤维蛋白原血症,临床应注意监测癫痫患儿凝血功能,发现低纤维蛋白原血症后及时处理,减少相关出血并发症.

Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

目的 观察清醒期、睡眠期婴儿痉挛症(infantile spasms,IS)患儿痉挛发作期间不同频段脑功能网络属性特征路径长度(characteristic path length,CPL)的变化,探讨激素冲击治疗对IS患儿脑功能网络的作用.方法 IS患儿19例(IS组),均行甲泼尼龙或促肾上腺皮质激素冲击治疗;记录IS组激素冲击治疗前、后清醒期、睡眠期、清醒发作期、睡眠发作期脑电图数据,应用matlab软件分析delta、theta、alpha、beta、gamma频段CPL.选取同期行视频脑电图检查结果正常的儿童10例为对照组,比较2组清醒期、睡眠期脑电图delta、theta、alpha、beta、gamma频段CPL.随访1年,观察IS患儿激素冲击治疗后痉挛发作的控制情况.结果 随访1年,痉挛发作完全控制11例,治疗无效8例.激素冲击治疗前IS组患儿清醒期脑电图delta频段CPL[130.79(121.61,144.74)×10-3]高于对照组[128.50(119.11,140.78)×10-3](Z=-2.645,P=0.008),beta、gamma 频段 CPL[89.72(78.65,65 535.00)×10-3、94.22(83.98,65 535.00)×10-3]均低于对照组[107.87(90.37,65 535.00)×10-3、98.33(88.53,65 535.00)×10-3](Z=-9.236,P＜0.001;Z=-3.282,P=0.001);睡眠期脑电图 delta、beta 频段 CPL[129.17(118.06,140.99)×10-3、82.80(74.14,113.68)×10-3]均低于对照组[131.90(122.48,141.69)×10-3、92.38(76.94,65 535.00)×10-3](Z=-2.688,P=0.007;Z=-5.079,P＜0.001).清醒期IS组患儿激素冲击治疗后脑电图beta、gamma频段CPL[94.37(83.64,65 535.00)×10-3、97.98(88.04,65 535.00)×10-3]均高于激素冲击治疗前(Z=-4.503,P＜0.001;Z=-3.611,P＜0.001);睡眠期IS组患儿激素冲击治疗后脑电图beta频段CPL[89.65(79.43,65 535.00)×10-3]高于激素冲击治疗前(Z=-7.311,P＜0.001).IS患儿激素冲击治疗后清醒发作期脑电图delta、alpha、beta、gamma频段CPL[111.73(106.44,117.92)×10-3、110.75(103.97,130.07)×10-3、81.35(74.07,97.43)×10-3、92.61(79.01,65 535.00)×10-3]均低于冲击治疗前[118.16(110.58,130.23)×10-3、115.19(104.83,162.77)×10-3、90.53(76.98,65 535.00)×10-3、96.17(82.78,65 535.00)×10-3](P＜0.05);睡眠发作期脑电图 delta 频段 CPL[116.50(109.31,128.12)×10-3]高于冲击治疗前[113.66(107.56,121.60)×10-3](Z=-4.412,P＜0.001),theta 频段 CPL[131.56(114.90,177.63)×10-3]低于冲击治疗前[153.11(127.55,65 535.00)×10-3](Z=-6.109,P＜0.001).结论 IS患儿清醒期、睡眠期脑电图beta频段传输效率增强,激素冲击治疗可降低发作间期beta频段、睡眠发作期delta频段的传输效率,增强清醒发作期delta、alpha、beta、gamma频段的传输效率,改善脑电图高峰失律、减少高频振荡募集可能.