发热诱导的学龄期儿童难治性癫癎性脑病的临床特点及预后分析

Fever-induced refractory epileptic encephalopathy in school-aged children： clinical features andoutcome a multicenter study on 13 children

目的总结并分析国内发热诱导的学龄期儿童难治性癫痫性脑病（FIRES）患儿的临床特点及预后。方法使用多中心回顾性的研究，分析2001至2010年间13例FIRES患儿的临床资料，并对患儿的预后进行随访，随访时间平均1．5年。结果13例入选的患儿发病前身体健康，学习成绩优异，患儿均在发热后出现了癫痫持续状态不经历静止期，直接进入难治性的癫痫发作。男女比例为6：7，发病中位年龄8．3岁。癫痫发作主要表现为部分性发作起源，9例患儿继发全身性发作。初次头颅MRI检查有10例MRI正常，3例有颅内囊肿；所有患儿均接受正规抗癫痫药物（中位5种）治疗，效果不佳，3例接受过麻醉药物治疗，8例入ICU进行监护治疗，1例在急性期死亡。随访期仅有1例在药物控制下无临床发作，曾经4次试停药，均又出现发作（追踪10年），其余11例均有难治性的癫痫发作；除1例放弃治疗外，余10例均口服3-4种抗癫痫药物。12例随访时行脑电图检查，7例示局灶或多灶性放电，6例表现为不对称的弥漫性慢波。11例在随访期复查了头颅MRI，1例出现了颞叶萎缩，其余患儿头颅MRI较急性期未见明显改变。存活的患儿中有9例智力低下，3例可以上学，但学习能力未恢复到发病前的水平。结论FIRES是一类发热后急性起病的恶性癫痫综合征，至今病因未明，无有效的治疗手段，患儿预后差，常遗留认知障碍。

Objective To analyze the clinical features and outcomes of fever-induced refractory epileptic encephalopathy in school-aged children （ FIRES ） in China. Method A retrospective muhicenter study on 13 FIRES patients was conducted. By collecting the medical data and follow up research of these patients, the clinical manifestations, clinical courses, investigations, treatments and outcomes of FIRES patients were analyzed. Result The 13 enrolled patients were previously healthy. The median age at onset was 8. 3 years. The male-to-female ratio was 6： 7. They exhibited with prolonged refractory status epilepticus after fever onset. All the patients presented with partial seizures, 9 of them had secondary generalized epilepsy; 12 patients had EEG data, 6 of them showed asymmetric diffused slow wave. Seven patients presented with focal or multifocal discharges mostly located in frontotemproal areas. In acute period, many seizures （up to 100） could occur each day. Between seizures, the patients were drowsy or even comatose. Neuroimaging demonstrated normal findings in 10 children. Classical anti-epileptic drugs （AED, 3 -7 kinds, median 5 ） were ineffective; 3 children received anesthesia treatment. Eight patients were admitted to ICU, 6 of them needed mechanical ventilation. One patient died 1 week after discharge. In follow up period, most patients were in a stable and chronic condition. Seizures were controlled by AED only in 1 child. Parents of 1 patient gave up all treatment but the patient still had seizure. Other 10 patients hadrefractory epilepsy that could not be controlled by 3 - 4 AEDs. We collected neuroimaging data of 11 patients in follow up period, 1 of the 9 previously normal patients exhibited temporal lobe atrophy, others did not show any change compared with that in acute phase. Only 3 of the 12 surviving patients retained normal cognitive level but all of them could not recover to pre-morbidity status. Conclusion FIRES is a devastating epileptic eneephalopathy with unknown cause. Different kinds of anti-epileptic treatments were given without satisfactory effect, even extensive treatment efforts including intensive care were unsuccessful. Thus the outcome is disastrous in most of the oreviouslv healthy children.