儿童噬血细胞综合征中枢神经系统病变临床分析

Clinical analysis of childhood hemophagocytic lymphohistiocytosis with CNS involvement

目的总结儿童噬血细胞综合征(HLH)中枢神经系统病变的临床表现、头颅MRI特点及治疗方案。方法回顾分析3例有中枢神经系统症状的HLH(CNS-HLH)患儿的临床表现、脑脊液检查结果、中枢神经系统影像学特点及治疗、转归。结果 (1)CNS-HLH于重症HLH(2例)或在HLH疾病进展时(2例)发生;(2)CNS-HLH临床主要表现为头痛、呕吐、嗜睡、昏迷及抽搐;(3)脑脊液检查见蛋白、淋巴细胞增高,1例发现噬血细胞;(4)头颅MRI表现为硬膜下积液及脑实质局灶性T2高信号;(5)以替尼泊苷(150 mg/m2,每周1次)替代标准HLH-2004方案中的依托泊苷(3例)及给予兔抗人胸腺细胞免疫球蛋白2.5mg/(kg.d),5 d(2例),CNS-HLH和全身症状缓解2例,治愈1例。结论 CNS-HLH通常发生在重症HLH,病情严重,进展快。其临床表现、脑脊液检查、头颅MRI改变等均缺乏特异性。可应用强免疫抑制剂如替尼泊苷及兔抗人胸腺细胞免疫球蛋白替代标准HLH-2004方案无法控制的高细胞因子风暴,为造血干细胞移植赢得时间。

Objective To summarize the （MRI）findings and treatment regimen in childhood clinical characteristics, magnetic resonance imaging hemophagocytic lymphohistiocytosis with central nervous system （CNS-HLH） involvement. Methods Clinical manifestations, cerebrospinal fluid （CSF） evaluations, brain MRI findings and prognosis in 3 CNS-HLH patients were reviewed retrospectively. Results （1） CNS-HLH was found in severe cases （2 cases） or cases with progressive systemic symptoms（2 cases） ; （2）Clinical manifestations were mainly presented by headache, nausea, somnolence, coma and convulsions; （3）CSF examination showed elevated protein and pleocytosis. Hemophagocyte was found in 1 case. （~） Brain MRI indicated subdural fluid accumulation and increased intensity of focal brain parenchyma on T2 weighed image. （4）After treatment of VM26（ 150 mg/m2, once per week） and ATG 2.5 mg/kg, d for 5 days, 2 patients obtained remission, and 1 patient was cured. Conclusions CNS-HLH often occurs in severe HLH cases, and develops progressively. Its clinical features, CSF findings and brain MRI results are aspecific. Strong cytokine storm could be controlled by immunosuppressants such as VM26 and ATG instead of HLH-2004 protocol, in order to earn more time for hematopoietic stem cell transplantation.