新生儿难治性惊厥的临床特征及预后相关因素

Clinical characteristics and prognostic indicators of neonatal refractory seizures

目的探讨新生儿难治性惊厥的病因和临床特点，分析影响预后的因素。方法选取2000年1月1日至2011年7月31日在北京大学第=医院新生儿病房住院的临床诊断难治性惊厥新生儿46例，选取同期收治非难治性惊厥的新生儿惊厥患儿42例作为对照组，比较2组的病因、临床特点及预后。难治性惊厥患儿预后正常11例，预后不良35例，比较2组的病因及临床特点。应用卡方检验比较组间差异；应用Logistic多元回归分析发展为难治性惊厥的危险因素和影响难治性惊厥患儿预后的危险因素。结果（1）难治性惊厥患儿常见的病因为严重的围产期脑损伤（8／46，17．4％），脑结构发育异常（7／46，15．2％）和先天性代谢性疾病（3／46，6．5％）。难治性惊厥患儿每日均有惊厥发作者占91．3％（42／46），脑电图重度异常者占55．6％（25／45），存在惊厥持续状态者占17．4％（8／46），预后不良者占76．1％（35／46），均明显高于非难治性惊厥患儿，分别为57．1％（24／42）、5．4％（2／37）、0．0％（0／42）和21．4％（9／42），差异均有统计学意义（y。分别为13．665、23．123、Fisher精确概率法、26．236，P均〈0．01）。脑电图重度异常（OR=16．384，95％CI：3．421～78．472，P：0．000）和每日均有惊厥发作（OR=3．811，95％CI：1．019～14．258，P=0．047）是发展为难治性惊厥的独立危险因素。（2）难治性惊厥患儿预后不良者苯巴比妥治疗无效的比例为80．0％（28／35），明显高于预后正常者的4／11，差异有统计学意义（Fisher精确概率法，P=0．010）。苯巴比妥治疗无效也提示难治性惊厥患儿预后不良（OR=12．444，95％CI：2．530～61．217，P=0．002）。结论新生儿难治性惊厥的常见病因为严重的围产期脑损伤、脑结构发育异常及先天性代谢性疾病。其临床表现以频繁发作、易存在惊厥持续状态及脑电图重度异常为特点，常预后不良，对苯巴比妥的治疗反应欠佳提示预后不良。

Objective To investigate the etiology, clinical characteristics and prognostic indicators of neonatal refractory seizures. Methods Forty-six newborns admitted to the neonatology ward of Peking University First Hospital from January 1, 2000 till July 31, 2011 with refractory seizures were chosen as the subject, and another 42 newborns with nonrefractory seizures who were admitted at the same period were chosen as the nonrefractory seizures group. The etiologies, clinical characteristics and prognosis of newborns in the two groups were compared. The newborns with refractory seizures were further divided into two subgroups： one was composed of 11 newborns with normal prognosis, and the other was composed of 35 newborns with unfavorable prognosis. The etiologies and clinical characteristics of seizure in thses two subgroups were also compared. Chi-square or Fisher＇s exact test was applied to compare the difference between groups; Logistic regression analysis was applied to determine the risk factors of refractory seizures and its prognosis. Results （1） The first three common causes of neonatal refractory seizures were severe perinatal brain damage （8/46, 17.4%）, encephalodysplasia （ 7/46, 15.2%） and congenital metabolic diseases （ 3/46, 6.5%）. Seizure attack every day, severe abnormal electroencephalogram, statural convulsivus and unfavorable prognosis were significantly higher in the refractory seizure group than that in the nonrefractoryseizures group E91. 3%0 （42/46） vs 57.1% （24/42） ; 55. 6% （25/45） vs 5.4%（2/37）; 17.4% （8/46） vs 0.0%（0/42） ; 76.1%（35/46） vs 21.4%（9/42）, Z2 =13. 665,23. 123,Fisher＇s exact test and 26.236,respectively, all P^0.01J. Seizure attack everyday （0R=3.811, 95%00CI： 1. 019- 14. 258, P = 0. 047） and severe abnormal electroencephalogram （OR = 16. 384, 95% CI： 3. 421- 78. 472,P=0. 000） were independent risk factors of refractory seizures. （2） Among those newborns with refractory seizures and unfavorable prognosis, the failure rate of phenobarbital administration was 80.0%（28/35）, higher than those with normal prognosis （4/11） （Fisher＇s exact test, P=0.010）. Therefore, poor phenobarbital therapeutic efficacy indicated an unfavorable prognosis （OR= 12. 444, 95%CI：2. 530 61. 217,P=0. 002）. Conclusions The common causes of neonatal refractory seizures are perinatal brain damage, encephalodysplasia and congenital metabolic diseases. The clinical characteristics of refractory seizure are frequent seizure attacks （more than once a day）, severe abnormal electroencephalogram and statural convulsivus, and unfavorable prognosis is common. Poor therapeutic effect of phenobarbital prompts adverse outcome.